aryl hydrocarbon receptors

Summary

Summary: Cytoplasmic proteins that bind certain aryl hydrocarbons, translocate to the nucleus, and activate transcription of particular DNA segments. AH receptors are identified by their high-affinity binding to several carcinogenic or teratogenic environmental chemicals including polycyclic aromatic hydrocarbons found in cigarette smoke and smog, heterocyclic amines found in cooked foods, and halogenated hydrocarbons including dioxins and polychlorinated biphenyls. No endogenous ligand has been identified, but an unknown natural messenger with a role in cell differentiation and development is suspected.

Top Publications

  1. ncbi Role of aryl hydrocarbon receptor-mediated induction of the CYP1 enzymes in environmental toxicity and cancer
    Daniel W Nebert
    Department of Environmental Health and Center for Environmental Genetics, University of Cincinnati Medical Center, Cincinnati, Ohio 45267 0056, USA
    J Biol Chem 279:23847-50. 2004
  2. ncbi The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins
    Marc Veldhoen
    Division of Molecular Immunology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW71AA, UK
    Nature 453:106-9. 2008
  3. ncbi Control of T(reg) and T(H)17 cell differentiation by the aryl hydrocarbon receptor
    Francisco J Quintana
    Center for Neurologic Diseases, Brigham and Women s Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA
    Nature 453:65-71. 2008
  4. ncbi Activation of the aryl hydrocarbon receptor by structurally diverse exogenous and endogenous chemicals
    Michael S Denison
    Department of Environmental Toxicology, University of California, Davis, California 95616, USA
    Annu Rev Pharmacol Toxicol 43:309-34. 2003
  5. ncbi Loss of teratogenic response to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in mice lacking the Ah (dioxin) receptor
    J Mimura
    Department of Chemistry, Graduate School of Science, Tohoku University, Sendai, Japan
    Genes Cells 2:645-54. 1997
  6. ncbi Dioxin receptor is a ligand-dependent E3 ubiquitin ligase
    Fumiaki Ohtake
    ERATO, Japan Science and Technology Agency, 4 1 8 Honcho, Kawaguchi, Saitama 332 0012, Japan
    Nature 446:562-6. 2007
  7. pmc Aryl hydrocarbon receptor regulates Stat1 activation and participates in the development of Th17 cells
    Akihiro Kimura
    Laboratory of Immune Regulation, Osaka University Graduate School of Frontier Biosciences, 1 3, Yamada oka, Suita, Osaka 565 0871, Japan
    Proc Natl Acad Sci U S A 105:9721-6. 2008
  8. ncbi Aryl-hydrocarbon receptor-deficient mice are resistant to 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced toxicity
    P M Fernandez-Salguero
    Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Toxicol Appl Pharmacol 140:173-9. 1996
  9. pmc The search for endogenous activators of the aryl hydrocarbon receptor
    Linh P Nguyen
    McArdle Laboratory for Cancer Research, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53706, USA
    Chem Res Toxicol 21:102-16. 2008
  10. ncbi Aryl hydrocarbon receptor regulates distinct dioxin-dependent and dioxin-independent gene batteries
    Nathalie Tijet
    Department of Pharmacology, Medical Sciences Building, University of Toronto, Toronto, Ontario M5S 1A8, Canada
    Mol Pharmacol 69:140-53. 2006

Detail Information

Publications315 found, 100 shown here

  1. ncbi Role of aryl hydrocarbon receptor-mediated induction of the CYP1 enzymes in environmental toxicity and cancer
    Daniel W Nebert
    Department of Environmental Health and Center for Environmental Genetics, University of Cincinnati Medical Center, Cincinnati, Ohio 45267 0056, USA
    J Biol Chem 279:23847-50. 2004
    ..In the future, use of "humanized" mouse lines, containing a human AHR or CYP1 allele in place of the orthologous mouse gene, is one likely approach to show that the AHR and the CYP1 enzymes in human behave similarly to that in mouse...
  2. ncbi The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins
    Marc Veldhoen
    Division of Molecular Immunology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW71AA, UK
    Nature 453:106-9. 2008
    ..AHR ligands may therefore represent co-factors in the development of autoimmune diseases...
  3. ncbi Control of T(reg) and T(H)17 cell differentiation by the aryl hydrocarbon receptor
    Francisco J Quintana
    Center for Neurologic Diseases, Brigham and Women s Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA
    Nature 453:65-71. 2008
    ..Thus, AHR regulates both T(reg) and T(H)17 cell differentiation in a ligand-specific fashion, constituting a unique target for therapeutic immunomodulation...
  4. ncbi Activation of the aryl hydrocarbon receptor by structurally diverse exogenous and endogenous chemicals
    Michael S Denison
    Department of Environmental Toxicology, University of California, Davis, California 95616, USA
    Annu Rev Pharmacol Toxicol 43:309-34. 2003
    ....
  5. ncbi Loss of teratogenic response to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in mice lacking the Ah (dioxin) receptor
    J Mimura
    Department of Chemistry, Graduate School of Science, Tohoku University, Sendai, Japan
    Genes Cells 2:645-54. 1997
    ..In contrast to the role of AhR in the regulatory mechanism of xenobiotic-metabolizing enzymes, there is no direct proof that the AhR is involved in the teratogenic effects of TCDD...
  6. ncbi Dioxin receptor is a ligand-dependent E3 ubiquitin ligase
    Fumiaki Ohtake
    ERATO, Japan Science and Technology Agency, 4 1 8 Honcho, Kawaguchi, Saitama 332 0012, Japan
    Nature 446:562-6. 2007
    ....
  7. pmc Aryl hydrocarbon receptor regulates Stat1 activation and participates in the development of Th17 cells
    Akihiro Kimura
    Laboratory of Immune Regulation, Osaka University Graduate School of Frontier Biosciences, 1 3, Yamada oka, Suita, Osaka 565 0871, Japan
    Proc Natl Acad Sci U S A 105:9721-6. 2008
    ..These results indicate that Ahr participates in Th17 cell differentiation through regulating Stat1 activation, a finding that constitutes additional mechanisms in the modulation of Th17 cell development...
  8. ncbi Aryl-hydrocarbon receptor-deficient mice are resistant to 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced toxicity
    P M Fernandez-Salguero
    Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Toxicol Appl Pharmacol 140:173-9. 1996
    ..The mechanism(s) responsible for these apparently receptor-independent processes remain unclear but may involve novel, alternative pathways for TCDD-induced toxicity...
  9. pmc The search for endogenous activators of the aryl hydrocarbon receptor
    Linh P Nguyen
    McArdle Laboratory for Cancer Research, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53706, USA
    Chem Res Toxicol 21:102-16. 2008
    ..In light of the essential function of the AHR in embryonic development, we discuss the candidacy of each of these compounds as physiologically important activators...
  10. ncbi Aryl hydrocarbon receptor regulates distinct dioxin-dependent and dioxin-independent gene batteries
    Nathalie Tijet
    Department of Pharmacology, Medical Sciences Building, University of Toronto, Toronto, Ontario M5S 1A8, Canada
    Mol Pharmacol 69:140-53. 2006
    ..Overall, our study identifies a wide range of genes that depend on the AHR, either for constitutive expression or for response to TCDD...
  11. ncbi The aryl hydrocarbon receptor sans xenobiotics: endogenous function in genetic model systems
    Brian J McMillan
    McArdle Laboratory for Cancer Research, University of Wisconsin Shool of Medicine and Public Health, Madison, Wisconsin, USA
    Mol Pharmacol 72:487-98. 2007
    ..In this literature review, we survey the emerging picture of endogenous AHR biology from work in the vertebrate and invertebrate model systems Mus musculus, Caenorhabditis elegans, and Drosophila melanogaster...
  12. ncbi Modulation of oestrogen receptor signalling by association with the activated dioxin receptor
    Fumiaki Ohtake
    The Institute of Molecular and Cellular Biosciences, University of Tokyo, 1 1 1 Yayoi, Bunkyo ku, Tokyo, 113 0032, Japan
    Nature 423:545-50. 2003
    ....
  13. ncbi Functional role of AhR in the expression of toxic effects by TCDD
    Junsei Mimura
    Department of Biomolecular Science, Graduate School of Life Science, Tohoku University, Aoba ku, 980 8578, Sendai, Japan
    Biochim Biophys Acta 1619:263-8. 2003
    ..We summarize the present knowledge about functional role of AhR in TCDD-induced biological effects...
  14. pmc Aryl hydrocarbon receptor (AhR) agonists suppress interleukin-6 expression by bone marrow stromal cells: an immunotoxicology study
    Brenda A Jensen
    Department of Environmental Health, Boston University School of Public Health, 715 Albany Street, Boston, MA 02118, USA
    Environ Health 2:16. 2003
    ..Here, we extend these studies to evaluate the potential for two prototypic AhR agonists, 7,12-dimethylbenz [a]anthracene (DMBA) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), to alter stromal cell cytokine responses...
  15. pmc Identification of a novel mechanism of regulation of Ah (dioxin) receptor function
    J Mimura
    Department of Chemistry, Graduate School of Science, Tohoku University, Aoba ku, Sendai 980 8578, Japan
    Genes Dev 13:20-5. 1999
    ..Thus, AhR and AhRR form a regulatory circuit in the xenobiotic signal transduction pathway and provide a novel mechanism of regulation of AhR function that may determine tissue-specific sensitivity to environmental pollutants...
  16. pmc Characterization of a murine Ahr null allele: involvement of the Ah receptor in hepatic growth and development
    J V Schmidt
    Department of Molecular Pharmacology, Northwestern University Medical School, Chicago, IL 60611, USA
    Proc Natl Acad Sci U S A 93:6731-6. 1996
    ....
  17. pmc Benzo[a]pyrene carcinogenicity is lost in mice lacking the aryl hydrocarbon receptor
    Y Shimizu
    Department of Pathology, Faculty of Medicine, University of Tokyo, 7 3 1 Hongo, Bunkyo ku, Tokyo, 113 0033, Japan
    Proc Natl Acad Sci U S A 97:779-82. 2000
    ..Thus the carcinogenic action of B[a]P may be determined primarily by AhR, a transcriptional regulator of the gene for CYP1A1. The results of the present study provide direct evidence that AhR is involved in carcinogenesis...
  18. ncbi Aryl hydrocarbon receptors: diversity and evolution
    Mark E Hahn
    Biology Department, Woods Hole Oceanographic Institution, Redfield 340, MS 32, 45 Water Street, MA 02543 1049, USA
    Chem Biol Interact 141:131-60. 2002
    ..Sensitivity to the developmental toxicity of dioxins and related chemicals may have had its origin in the evolution of dioxin-binding capacity of the AHR in the vertebrate lineage...
  19. ncbi Ah receptor: dioxin-mediated toxic responses as hints to deregulated physiologic functions
    Karl Walter Bock
    Department of Toxicology, Institute of Pharmacology and Toxicology, University of Tubingen, Tubingen, Germany
    Biochem Pharmacol 72:393-404. 2006
    ..Though important issues remain unresolved, the commentary is intended to stimulate efforts to understand dioxin-mediated toxic responses with emphasis on carcinogenesis in comparison with AhR-mediated physiologic functions...
  20. pmc Portosystemic shunting and persistent fetal vascular structures in aryl hydrocarbon receptor-deficient mice
    G P Lahvis
    McArdle Laboratory for Cancer Research, University of Wisconsin Medical School, Madison, WI 53706, USA
    Proc Natl Acad Sci U S A 97:10442-7. 2000
    ....
  21. ncbi Novel compound 2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazo-phenyl)-amide (CH-223191) prevents 2,3,7,8-TCDD-induced toxicity by antagonizing the aryl hydrocarbon receptor
    Sun Hee Kim
    School of Environmental Science and Engineering, Pohang University of Science and Technology, Pohang 790 784, South Korea
    Mol Pharmacol 69:1871-8. 2006
    ..Taken together, these results demonstrate that this novel compound, CH-223191, may be a useful agent for the study of AhR-mediated signal transduction and the prevention of TCDD-associated pathology...
  22. ncbi Dietary flavonoids modulate PCB-induced oxidative stress, CYP1A1 induction, and AhR-DNA binding activity in vascular endothelial cells
    Pachaikani Ramadass
    Molecular and Cell Nutrition Laboratory, College of Agriculture, University of Kentucky, Lexington 40546 0215, USA
    Toxicol Sci 76:212-9. 2003
    ..These data suggest that protective effects of EGCG and quercetin are initiated upstream from CYP1A1 and that these flavonoids may be of value for inhibiting the toxic effects of PCBs on vascular endothelial cells...
  23. pmc The hsp90 chaperone complex regulates intracellular localization of the dioxin receptor
    A Kazlauskas
    Department of Cell and Molecular Biology, Medical Nobel Institute, Karolinska Institutet, S 171 77 Stockholm, Sweden
    Mol Cell Biol 21:2594-607. 2001
    ..In conclusion, these data suggest a novel role of the hsp90 molecular chaperone complex in regulation of the intracellular localization of the dioxin receptor...
  24. ncbi Molecular interactions of the aryl hydrocarbon receptor and its biological and toxicological relevance for reproduction
    P Pocar
    Department of Anatomy and Cell Biology, Faculty of Medicine, Martin Luther University Halle Wittenberg, Grosse Steinstrasse 52, D 06097, Halle Saale, Germany
    Reproduction 129:379-89. 2005
    ....
  25. ncbi Expression of aryl hydrocarbon receptor repressor in normal human tissues and inducibility by polycyclic aromatic hydrocarbons in human tumor-derived cell lines
    Yuki Tsuchiya
    Division of Drug Metabolism, Faculty of Pharmaceutical Sciences, Kanazawa University, Takara machi 13 1, Kanazawa 920 0934, Japan
    Toxicol Sci 72:253-9. 2003
    ..The chemical-specific inducibility of AhRR was also similar to that of the CYP1 family determined in our previous study. These results indicated that AhRR is also induced in chemical- and cell-specific manners...
  26. ncbi Differential regulation of cytochrome P450 1A1 and 1B1 by a combination of dioxin and pesticides in the breast tumor cell line MCF-7
    X Coumoul
    , , , France
    Cancer Res 61:3942-8. 2001
    ..These results show that xenoestrogens, by altering the ratio of CYP1B1/CYP1A1, could redirect estradiol metabolism in a more toxic pathway in the breast cell line MCF-7...
  27. pmc The aryl hydrocarbon receptor mediates degradation of estrogen receptor alpha through activation of proteasomes
    Mark Wormke
    Department of Veterinary Physiology and Pharmacology, Texas A and M University, College Station, TX 77843 4466, USA
    Mol Cell Biol 23:1843-55. 2003
    ....
  28. ncbi Identification of aryl hydrocarbon receptor as a putative Wnt/beta-catenin pathway target gene in prostate cancer cells
    Dennis R Chesire
    Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
    Cancer Res 64:2523-33. 2004
    ..Considering previous work linking AhR to processes of development and carcinogenesis, our data may highlight one particular role for wnt/beta-catenin signaling in prostate tumor biology...
  29. ncbi Aromatic hydrocarbon receptor interaction with the retinoblastoma protein potentiates repression of E2F-dependent transcription and cell cycle arrest
    A Puga
    Center for Environmental Genetics, Department of Environmental Health, University of Cincinnati Medical Center, Cincinnati, Ohio 45267 0056, USA
    J Biol Chem 275:2943-50. 2000
    ....
  30. pmc The aryl hydrocarbon receptor cross-talks with multiple signal transduction pathways
    Alvaro Puga
    Department of Environmental Health and Center for Environmental Genetics, University of Cincinnati College of Medicine, Cincinnati, OH 45220, USA
    Biochem Pharmacol 77:713-22. 2009
    ..Ultimately, the effect of a particular AHR ligand may depend as much on the adaptive interactions that it established with pathways and proteins expressed in a specific cell or tissue as on the toxic responses that it raises...
  31. ncbi Temporal and dose-dependent hepatic gene expression patterns in mice provide new insights into TCDD-Mediated hepatotoxicity
    Darrell R Boverhof
    Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing Michigan 48824 1319, USA
    Toxicol Sci 85:1048-63. 2005
    ..Collectively, the data support a proposed mechanism for TCDD-mediated hepatotoxicity, including fatty liver, which involves mobilization of peripheral fat and inappropriate increases in hepatic uptake of fatty acids...
  32. pmc Stepping backward to improve assessment of PCB congener toxicities
    L G Hansen
    Department of Veterinary Biosciences, University of Illinois, Urbana 61802, USA
    Environ Health Perspect 106:171-89. 1998
    ..A more comprehensive list of PCB congeners is proposed that would provide more adequate data upon which to base associations with adverse outcomes...
  33. pmc RelB, a new partner of aryl hydrocarbon receptor-mediated transcription
    Christoph F A Vogel
    Department of Environmental Toxicology, University of California, Davis, One Shields Avenue, Davis, California 95616, USA
    Mol Endocrinol 21:2941-55. 2007
    ..The interaction of RelB with AhR signaling, and AhR with NF-kappaB RelB signaling pathways represent a new mechanism of cross talk between the two transcription factors...
  34. pmc The role of the aryl hydrocarbon receptor in the female reproductive system
    Isabel Hernández-Ochoa
    Department of Veterinary Biosciences, University of Illinois Urbana Champaign, Urbana, IL 61802, USA
    Biochem Pharmacol 77:547-59. 2009
    ....
  35. ncbi Role of the aromatic hydrocarbon receptor and [Ah] gene battery in the oxidative stress response, cell cycle control, and apoptosis
    D W Nebert
    Department of Environmental Health and the Center for Environmental Genetics, University of Cincinnati Medical Center, OH 45267 0056, USA
    Biochem Pharmacol 59:65-85. 2000
    ..These proposed endogenous functions of the AHR and [Ah] enzymes are, of course, in addition to the frequently described functions of "metabolic potentiation" and "detoxification" of various foreign chemicals...
  36. ncbi The RelA NF-kappaB subunit and the aryl hydrocarbon receptor (AhR) cooperate to transactivate the c-myc promoter in mammary cells
    D W Kim
    Department of Biochemistry, Women s Health, Boston University School of Medicine, Massachusetts 02118, USA
    Oncogene 19:5498-506. 2000
    ..These findings suggest a novel signaling mechanism whereby the Ah receptor can stimulate proliferation and tumorigenesis of mammary cells...
  37. ncbi Activation of the Ah receptor signaling pathway by prostaglandins
    S D Seidel
    Department of Environmental Toxicology, University of California, Davis, 95616-8588, USA
    J Biochem Mol Toxicol 15:187-96. 2001
    ..Overall, our results demonstrate that selected prostaglandins are weak agonists for the AhR and they represent a structurally distinct and novel class of activator of the AhR signal transduction pathway...
  38. ncbi The aryl hydrocarbon receptor in immunity
    Charlotte Esser
    Institut fur Umweltmedizinische Forschung, Auf m Hennekamp 50, 40225 Dusseldorf, Germany
    Trends Immunol 30:447-54. 2009
    ..In particular, Th17 cells and dendritic cells express high levels of AhR. We review here current evidence for the physiological role of AhR in the immune system, focussing in particular on T-cell biology...
  39. ncbi Point mutation in intron sequence causes altered carboxyl-terminal structure in the aryl hydrocarbon receptor of the most 2,3,7,8-tetrachlorodibenzo-p-dioxin-resistant rat strain
    R Pohjanvirta
    National Public Health Institute, Department of Environmental Medicine, FIN 70701 Kuopio, Finland
    Mol Pharmacol 54:86-93. 1998
    ..These findings suggest that there is a relatively small region in the AhR trans-activation domain that may be capable of providing selectivity to its function...
  40. pmc Regulation of constitutive and inducible AHR signaling: complex interactions involving the AHR repressor
    Mark E Hahn
    Biology Department, Woods Hole Oceanographic Institution, Woods Hole, MA, USA
    Biochem Pharmacol 77:485-97. 2009
    ..Collectively, this discussion emphasizes the importance of this understudied bHLH-PAS protein in tissue development, normal cell biology, xenobiotic responsiveness, and AHR-regulated malignancy...
  41. ncbi Cloning of a factor required for activity of the Ah (dioxin) receptor
    E C Hoffman
    Department of Pathology, University of California, Los Angeles 90024
    Science 252:954-8. 1991
    ..Another segment of the protein shows conformity to the consensus sequence for the basic helix-loop-helix motif found in proteins that bind DNA as homodimers or heterodimers...
  42. pmc Agonist and chemopreventative ligands induce differential transcriptional cofactor recruitment by aryl hydrocarbon receptor
    Eli V Hestermann
    Department of Molecular Oncology, Dana Farber Cancer Institute, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts, USA
    Mol Cell Biol 23:7920-5. 2003
    ..This novel mechanism of receptor antagonism may account for the antitumor properties of chemopreventative compounds targeting the AHR...
  43. ncbi Identification of the tryptophan photoproduct 6-formylindolo[3,2-b]carbazole, in cell culture medium, as a factor that controls the background aryl hydrocarbon receptor activity
    Mattias Oberg
    Institute of Environmental Medicine, Karolinska Institutet, SE 171 77 Stockholm, Sweden
    Toxicol Sci 85:935-43. 2005
    ..These results clearly show that tryptophan derived AhR ligands, which have been suggested to be endogenous AhR ligands, influence the background levels of CYP1A1 activity in cells in culture...
  44. ncbi Aryl hydrocarbon receptor 2 mediates 2,3,7,8-tetrachlorodibenzo-p-dioxin developmental toxicity in zebrafish
    Amy L Prasch
    Molecular and Environmental Toxicology Center, University of Wisconsin, Madison, Wisconsin 53726, USA
    Toxicol Sci 76:138-50. 2003
    ..Most strikingly, zfahr2 morphants exposed to TCDD never developed edema. Taken together, these results demonstrate that zfAHR2 mediates several endpoints of TCDD developmental toxicity in zebrafish...
  45. ncbi Inhibitory aryl hydrocarbon receptor-estrogen receptor alpha cross-talk and mechanisms of action
    Stephen Safe
    Department of Veterinary Physiology and Pharmacology, Texas A and M University, College Station, Texas 77843 4466, USA
    Chem Res Toxicol 16:807-16. 2003
  46. ncbi Aryl hydrocarbon receptor expression and activity in cerebellar granule neuroblasts: implications for development and dioxin neurotoxicity
    Mary A Williamson
    Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA
    Toxicol Sci 83:340-8. 2005
    ..These data suggest that (1) granule neuroblasts are direct targets for developmental AhR-mediated TCDD neurotoxicity and (2) TCDD exposure may disrupt granule cell neurogenesis...
  47. pmc Hepatitis B virus X-associated protein 2 is a subunit of the unliganded aryl hydrocarbon receptor core complex and exhibits transcriptional enhancer activity
    B K Meyer
    Graduate Program in Biochemistry and Molecular Biology, The Pennsylvania State University, University Park 16802, USA
    Mol Cell Biol 18:978-88. 1998
    ..XAP2 enhanced the ability of endogenous murine and human AhR complexes to activate a dioxin-responsive element-luciferase reporter twofold, following transient expression of XAP2 in Hepa 1c1c7 and HeLa cells...
  48. ncbi Identification of the Ah receptor nuclear translocator protein (Arnt) as a component of the DNA binding form of the Ah receptor
    H Reyes
    Department of Pathology, University of California, Los Angeles 90024
    Science 256:1193-5. 1992
    ..Arnt contains a basic helix-loop-helix motif, which may be responsible for interacting with both the XRE and the ligand-binding subunit...
  49. pmc Aryl hydrocarbon receptor-dependent liver development and hepatotoxicity are mediated by different cell types
    Jacqueline A Walisser
    McArdle Laboratory for Cancer Research, University of Wisconsin Medical School, Madison, WI 53706, USA
    Proc Natl Acad Sci U S A 102:17858-63. 2005
    ..Taken together, these data illustrate the importance of cell-specific receptor signaling for the generation of distinct AHR-dependent physiological outcomes...
  50. pmc The aryl hydrocarbon receptor binds to E2F1 and inhibits E2F1-induced apoptosis
    Jennifer L Marlowe
    Department of Environmental Health and Center for Environmental Genetics, University of Cincinnati College of Medicine, Cincinnati, OH 45267 0056, USA
    Mol Biol Cell 19:3263-71. 2008
    ..These results point to a proproliferative, antiapoptotic function of the Ah receptor that likely plays a role in tumor progression...
  51. ncbi Tamoxifen-induced antitumorigenic/antiestrogenic action synergized by a selective aryl hydrocarbon receptor modulator
    A McDougal
    Department of Veterinary Physiology and Pharmacology, Texas A and M University, College Station, TX 77843, USA
    Cancer Res 61:3902-7. 2001
    ....
  52. ncbi Unexpected diversity of aryl hydrocarbon receptors in non-mammalian vertebrates: insights from comparative genomics
    Mark E Hahn
    Biology Department, Woods Hole Oceanographic Institution, Woods Hole, Massachusetts, USA
    J Exp Zool A Comp Exp Biol 305:693-706. 2006
    ....
  53. ncbi Regulation of preB cell apoptosis by aryl hydrocarbon receptor/transcription factor-expressing stromal/adherent cells
    R I Near
    Department of Environmental Health, Boston University Schools of Medicine and Public Health, Boston, Massachusetts 02118, USA
    Proc Soc Exp Biol Med 221:242-52. 1999
    ..Collectively, the data indicated that AhR-regulated activities in the hematopoietic microenvironment influence the susceptibility of immature lymphocytes to low-dose PAH exposure...
  54. ncbi Differential recruitment of coactivator RIP140 by Ah and estrogen receptors. Absence of a role for LXXLL motifs
    M B Kumar
    Center for Molecular Toxicology, Pennsylvania State University, University Park, Pennsylvania 16802, USA
    J Biol Chem 274:22155-64. 1999
    ..In addition, the data suggest that there are distinct motif(s) for the recruitment of RIP140 to AhR and possibly other non-steroid receptors/transcription factors...
  55. pmc A new cross-talk between the aryl hydrocarbon receptor and RelB, a member of the NF-kappaB family
    Christoph F A Vogel
    Department of Environmental Toxicology, University of California Davis, Davis, CA 95616, USA
    Biochem Pharmacol 77:734-45. 2009
    ..Based on such information, a hypothesis has been proposed in this review that AhR together with RelB functions as a coordinator of inflammatory responses...
  56. pmc Inflammatory signaling and aryl hydrocarbon receptor mediate synergistic induction of interleukin 6 in MCF-7 cells
    Brett D Hollingshead
    Department of Veterinary and Biomedical Sciences and Center for Molecular Toxicology and Carcinogenesis, Pennsylvania State University, University Park, Pennsylvania, USA
    Cancer Res 68:3609-17. 2008
    ..The data also suggest a possible previously unrecognized mechanism of AHR-mediated tumor promotion...
  57. ncbi Correlation of cardiotoxicity mediated by halogenated aromatic hydrocarbons to aryl hydrocarbon receptor activation
    S E Heid
    Department of Pharmacology, University of Kentucky Medical Center, Lexington, Kentucky 40536, USA
    Toxicol Sci 61:187-96. 2001
    ..These results indicate that the ability of HAHs to activate the avian AHR signaling pathway, in general, correlates with their ability to mediate cardiotoxicity in the chick embryo...
  58. pmc Constitutive expression of aryl hydrocarbon receptor in keratinocytes causes inflammatory skin lesions
    Masafumi Tauchi
    Graduate School of Comprehensive Human Sciences and Center for Tsukuba Advanced Research Alliance TARA, University of Tsukuba, 1 1 1 Tennoudai, Tsukuba 305 8577, Japan
    Mol Cell Biol 25:9360-8. 2005
    ..We demonstrate that constitutive activation of the AhR pathway causes inflammatory skin lesions and suggests a new mechanism for the exacerbation of inflammatory diseases after exposure to occupational and environmental xenobiotics...
  59. ncbi A role of aryl hydrocarbon receptor in the antiandrogenic effects of polycyclic aromatic hydrocarbons in LNCaP human prostate carcinoma cells
    Ryoichi Kizu
    Graduate School of Natural Science and Technology, Kanazawa University, 13 1 Takara machi, Kanazawa 920 0934, Japan
    Arch Toxicol 77:335-43. 2003
    ..These results suggest that AhR can stimulate AP-1 expression resulting in inhibition of the binding of AR to ARE in the transcription regulatory region of target genes such as PSA...
  60. ncbi The aryl hydrocarbon receptor: studies using the AHR-null mice
    F J Gonzalez
    Division of Basic Sciences, National Cancer Institute, Bethesda, MD 20892, USA
    Drug Metab Dispos 26:1194-8. 1998
    ..AHR may directly or indirectly control levels of a cytochrome P450 that is responsible for catabolizing retinoic acid...
  61. ncbi Low-dose dioxins alter gene expression related to cholesterol biosynthesis, lipogenesis, and glucose metabolism through the aryl hydrocarbon receptor-mediated pathway in mouse liver
    Shoko Sato
    Laboratory of Nutrition, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan
    Toxicol Appl Pharmacol 229:10-9. 2008
    ..These results indicate that changes in gene expression by TCDD are mediated by AHR and that exposure to low-dose TCDD could affect energy metabolism via alterations of gene expression...
  62. ncbi Identification of functional domains of the aryl hydrocarbon receptor
    B N Fukunaga
    Department of Pathology and Laboratory Medicine, University of California, Los Angeles 90095 1786, USA
    J Biol Chem 270:29270-8. 1995
    ....
  63. ncbi The AH-receptor: genetics, structure and function
    H I Swanson
    Department of Pharmacology, Northwestern University Medical School, Chicago, IL 60611
    Pharmacogenetics 3:213-30. 1993
    ..The objectives of this review are to describe recent experimental results in this field and to use this information to develop a molecular model of AH-receptor mediated signal transduction...
  64. ncbi Immune system impairment and hepatic fibrosis in mice lacking the dioxin-binding Ah receptor
    P Fernandez-Salguero
    Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Science 268:722-6. 1995
    ..Thus, the AHR plays an important role in the development of the liver and the immune system...
  65. ncbi PD98059 is an equipotent antagonist of the aryl hydrocarbon receptor and inhibitor of mitogen-activated protein kinase kinase
    J J Reiners
    Institute of Chemical Toxicology, Wayne State University, Detroit, Michigan 48201, USA
    Mol Pharmacol 53:438-45. 1998
    ..These results suggest that PD98059 is a ligand for the AHR and functions as an AHR antagonist at concentrations commonly used to inhibit MEK and signaling processes that entail MEK activation...
  66. ncbi Analysis of the four alleles of the murine aryl hydrocarbon receptor
    A Poland
    McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, 53706
    Mol Pharmacol 46:915-21. 1994
    ..Using 5' truncation and mutations to produce 3' translation truncation sites, we mapped the ligand binding region for the Ahb-1 allele...
  67. ncbi Fetal growth restriction triggered by polycyclic aromatic hydrocarbons is associated with altered placental vasculature and AhR-dependent changes in cell death
    Jacqui Detmar
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario, Canada
    Am J Physiol Endocrinol Metab 295:E519-30. 2008
    ..The results of this investigation suggest that chronic exposure to PAHs is a contributing factor to the development of IUGR in human smokers and that the AhR pathway is involved...
  68. pmc The zebrafish (Danio rerio) aryl hydrocarbon receptor type 1 is a novel vertebrate receptor
    Eric A Andreasen
    Environmental Toxicology Center, University of Wisconsin, Madison, Wisconsin, USA
    Mol Pharmacol 62:234-49. 2002
    Fish are known to have two distinct classes of aryl hydrocarbon receptors, and their roles in mediating xenobiotic toxicity remain unclear...
  69. ncbi Developmental expression of two members of a new class of transcription factors: I. Expression of aryl hydrocarbon receptor in the C57BL/6N mouse embryo
    B D Abbott
    Developmental Toxicology Division, U S Environmental Protection Agency, Research Triangle Park, NC 27711, USA
    Dev Dyn 204:133-43. 1995
    ..AhR expression was specific for both cell type, organ/tissue, and developmental stage, suggesting that this novel ligand-activated transcriptional regulator may be important in normal embryonic development...
  70. pmc Impact of polychlorinated biphenyls contamination on estrogenic activity in human male serum
    Martina Plísková
    Veterinary Research Institute, Brno, Czech Republic
    Environ Health Perspect 113:1277-84. 2005
    ..Our data also suggest that it might be important to pay attention to direct effects of PCBs on steroid hormone levels in heavily exposed subjects...
  71. ncbi Structure and expression of the Ah receptor repressor gene
    T Baba
    Department of Biomolecular Science, Graduate School of Life Science, Tohoku University, Sendai 980 8578, Japan
    J Biol Chem 276:33101-10. 2001
    ....
  72. pmc Intrinsic function of the aryl hydrocarbon (dioxin) receptor as a key factor in female reproduction
    Takashi Baba
    Department of Developmental Biology, National Institute for Basic Biology, Okazaki, Aichi, Japan
    Mol Cell Biol 25:10040-51. 2005
    ..In addition to elucidating a physiological function for AhR, our studies also suggest a possible mechanism for the toxic effects of exogenous AhR ligands as endocrine disruptors...
  73. pmc Distinct response to dioxin in an arylhydrocarbon receptor (AHR)-humanized mouse
    Takashi Moriguchi
    Institute of Basic Medical Sciences, Center for Tsukuba Advanced Research Alliance, and Exploratory Research for Advanced Technology Environmental Response Project, University of Tsukuba, Tsukuba 305 8575, Japan
    Proc Natl Acad Sci U S A 100:5652-7. 2003
    ..Thus, the hAHR knock-in mouse is a humanized model mouse that may better predict the biological effects of bioaccumulative environmental toxicants like TCDD in humans...
  74. ncbi High levels of dioxin-like potential in cigarette smoke evidenced by in vitro and in vivo biosensing
    Ayumi Kasai
    Department of Molecular Signaling, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan
    Cancer Res 66:7143-50. 2006
    ..These results evidenced for the first time that cigarette smoke has unexpectedly high dioxin-like potential that triggers the AhR-XRE pathway in vitro and in vivo...
  75. ncbi Physiological role of the aryl hydrocarbon receptor in mouse ovary development
    J C Benedict
    Program in Toxicology and Department of Epidemiology and Preventive Medicine, University of Maryland, Baltimore 21201, USA
    Toxicol Sci 56:382-8. 2000
    ..wild-type = 6776 +/- 1024). Taken together, these results suggest that the AhR may play a role in the formation of primordial follicles and the regulation of antral follicle numbers...
  76. ncbi The aryl hydrocarbon receptor and light
    Agneta Rannug
    Karolinska Institute, Institute of Environmental Medicine, P O Box 210, S 171 77 Stockholm, Sweden
    Biol Chem 387:1149-57. 2006
    ..We discuss the involvement of the AhR in different biological rhythms and speculate on the possible role of the AhR in UV-induced responses in skin. Furthermore, this review points out future research needs in this field...
  77. pmc Aryl hydrocarbon receptor in combination with Stat1 regulates LPS-induced inflammatory responses
    Akihiro Kimura
    Laboratory of Immune Regulation, Osaka University Graduate School of Frontier Biosciences, Suita, Osaka 565 0871, Japan
    J Exp Med 206:2027-35. 2009
    ..Ahr thus plays an essential role in the negative regulation of the LPS signaling pathway through interaction with Stat1...
  78. ncbi Resveratrol inhibits transcription of CYP1A1 in vitro by preventing activation of the aryl hydrocarbon receptor
    H P Ciolino
    Cellular Defense and Carcinogenesis Section, Basic Research Laboratory, Divsion of Basic Sciences, National Cancer Institute Frederick Cancer Research and Development Center, NIH, Maryland 21702 1201, USA
    Cancer Res 58:5707-12. 1998
    ..This activity may be an important part of the chemopreventive activity of resveratrol...
  79. ncbi The immune phenotype of AhR null mouse mutants: not a simple mirror of xenobiotic receptor over-activation
    Charlotte Esser
    Institut fur Umweltmedizinische Forschung, Division of Molecular Immunology, Dusseldorf, Germany
    Biochem Pharmacol 77:597-607. 2009
    ..In this review I look at the natural immunological function(s) of the AhR...
  80. pmc Intensity-based hierarchical Bayes method improves testing for differentially expressed genes in microarray experiments
    Maureen A Sartor
    Department of Environmental Health, University of Cincinnati, Cincinnati, OH, USA
    BMC Bioinformatics 7:538. 2006
    ....
  81. ncbi Oncogenic signaling pathways activated in DMBA-induced mouse mammary tumors
    Nicolas Currier
    Boston University School of Medicine, Department of Medicine, Boston, MA, USA
    Toxicol Pathol 33:726-37. 2005
    ..These data suggest that environmental carcinogens can produce long-lasting alterations in growth and anti-apoptotic pathways, leading to mammary tumorigenesis...
  82. pmc The aryl hydrocarbon receptor is a modulator of anti-viral immunity
    Jennifer L Head
    Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14620, USA
    Biochem Pharmacol 77:642-53. 2009
    ..While AhR clearly modulates host responses to viral infection, we still have much to understand about the complex interactions between immune cells, viruses, and the host environment...
  83. ncbi A novel cytoplasmic protein that interacts with the Ah receptor, contains tetratricopeptide repeat motifs, and augments the transcriptional response to 2,3,7,8-tetrachlorodibenzo-p-dioxin
    Q Ma
    Department of Molecular Pharmacology, Stanford University School of Medicine, Stanford, California 94305 5332, USA
    J Biol Chem 272:8878-84. 1997
    ..Overexpression of AIP augments the response of the CYP1A1 gene to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Our data suggest that AIP influences ligand receptivity and/or nuclear targeting of AhR...
  84. ncbi A novel effect of dioxin: exposure during pregnancy severely impairs mammary gland differentiation
    Beth A Vorderstrasse
    Department of Pharmaceutical Sciences, Washington State University, Pullman, Washington 99164, USA
    Toxicol Sci 78:248-57. 2004
    ....
  85. ncbi Patterns of dioxin-altered mRNA expression in livers of dioxin-sensitive versus dioxin-resistant rats
    Monique A Franc
    Department of Pharmacology and Toxicology, Medical Sciences Building, University of Toronto, Toronto, ON, Canada
    Arch Toxicol 82:809-30. 2008
    ..Type-II genes may lie in pathways that are central to the difference in susceptibility to TCDD lethality in this animal model...
  86. ncbi Expression of genes in the TGF-beta signaling pathway is significantly deregulated in smooth muscle cells from aorta of aryl hydrocarbon receptor knockout mice
    Junhai Guo
    Division of Biostatistics and Epidemiology, University of Cincinnati, OH 45267 0056, USA
    Toxicol Appl Pharmacol 194:79-89. 2004
    ..The above results provide a possible explanation for some of the multiple biological effects of TCDD and the physiological role played by the AHR in the absence of environmental agents...
  87. pmc Stochastic spineless expression creates the retinal mosaic for colour vision
    Mathias F Wernet
    Center for Developmental Genetics, Department of Biology, New York University, 100 Washington Place, New York, New York 10003, USA
    Nature 440:174-80. 2006
    ..Therefore, this study suggests that the entire retinal mosaic required for colour vision is defined by the stochastic expression of a single transcription factor, Spineless...
  88. ncbi Induction and superinduction of 2,3,7,8-tetrachlorodibenzo-rho-dioxin-inducible poly(ADP-ribose) polymerase: role of the aryl hydrocarbon receptor/aryl hydrocarbon receptor nuclear translocator transcription activation domains and a labile transcription r
    Qiang Ma
    Receptor Biology Laboratory, Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, WV 26505, USA
    Arch Biochem Biophys 404:309-16. 2002
    ....
  89. ncbi The aryl hydrocarbon receptor, more than a xenobiotic-interacting protein
    Robert Barouki
    INSERM, UMR S 747, 75270 Paris Cedex 06, France
    FEBS Lett 581:3608-15. 2007
    ..In this review, we will attempt to summarize the studies supporting the implication of the AhR in those endogenous cellular processes...
  90. ncbi Bioanalytical screening methods for dioxins and dioxin-like compounds a review of bioassay/biomarker technology
    P A Behnisch
    Life Science Research Laboratories, Kaneka Corporation, Takasago, Japan
    Environ Int 27:413-39. 2001
    ..The relative potencies (REPs) to 2,3,7,8-TCDD for dioxin-like compounds are reviewed for various BDMs and the differences are noted...
  91. ncbi Mechanisms of inhibitory aryl hydrocarbon receptor-estrogen receptor crosstalk in human breast cancer cells
    S Safe
    Department of Veterinary Physiology and Pharmacology, Texas A and M University, College Station 77843 4466, USA
    J Mammary Gland Biol Neoplasia 5:295-306. 2000
    ....
  92. pmc Aryl hydrocarbon receptor suppresses intestinal carcinogenesis in ApcMin/+ mice with natural ligands
    Kaname Kawajiri
    Research Institute for Clinical Oncology and Hospital, Saitama Cancer Center, 818 Komuro, Ina, Saitama, 362 0806, Japan
    Proc Natl Acad Sci U S A 106:13481-6. 2009
    ..These findings suggest that chemoprevention with naturally-occurring and chemically-designed AhR ligands can be used to successfully prevent intestinal cancers...
  93. pmc AHR-mediated immunomodulation: the role of altered gene transcription
    Nancy I Kerkvliet
    Department of Environmental and Molecular Toxicology and Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331, USA
    Biochem Pharmacol 77:746-60. 2009
    ..Based on studies using AHR(-/-) mice, evidence for a role of endogenous AHR ligands in regulation of the immune response is growing, with bilirubin and lipoxinA4 representing two promising candidates...
  94. ncbi Interactions of nuclear receptor coactivator/corepressor proteins with the aryl hydrocarbon receptor complex
    T A Nguyen
    Department of Veterinary Physiology and Pharmacology, Texas A and M University, College Station, Texas, 77843 4466, USA
    Arch Biochem Biophys 367:250-7. 1999
    ..These results confirmed functional and physical interactions of AhR/Arnt with ERAP 140 and SMRT in breast cancer cells...
  95. ncbi Ligand-dependent and independent modulation of aryl hydrocarbon receptor localization, degradation, and gene regulation
    Zhijuan Song
    Department of Biology, University of South Florida, Tampa, Florida, USA
    Mol Pharmacol 62:806-16. 2002
    ....
  96. pmc Dietary polyphenols increase paraoxonase 1 gene expression by an aryl hydrocarbon receptor-dependent mechanism
    Cédric Gouédard
    INSERM UMR S 490, Université Renes Descartes, 75270 Paris Cedex 06, France
    Mol Cell Biol 24:5209-22. 2004
    ..These observations provide a molecular mechanism for the regulation of the cardioprotective enzyme PON-1 by polyphenols. They suggest also that AhR ligands may differentially regulate gene expression depending on the DNA target sequence...
  97. ncbi HES-1, a novel target gene for the aryl hydrocarbon receptor
    Jane Sohn Thomsen
    Department of Biosciences at Novum, Karolinska Institutet, Huddinge, Sweden
    Mol Pharmacol 65:165-71. 2004
    ..Our observation that both the estrogen receptor and AhR signaling pathways regulate HES-1, but with opposing effects, suggests the existence of a new pathway by which AhR represses E2-signaling...
  98. ncbi Over-production of IFN-gamma and IL-12 in AhR-null mice
    Miriam Rodriguez-Sosa
    Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autonoma de Mexico, C P 54090 Estado de México, Mexico
    FEBS Lett 579:6403-10. 2005
    ..These data suggest that AhR may play an important role in the normal development and function of immune system by down-regulating IFN-gamma and IL-12 expression...
  99. ncbi Effects of o,p'-DDT on the 2,3,7,8-tetrachlorodibenzo-p-dioxin-inducible CYP1A1 expression in murine Hepa-1c1c7 cells
    Hye Gwang Jeong
    Department of Pharmacy, College of Pharmacy, Research Center for Proteineous Materials, Chosun University, Kwangju, South Korea
    Food Chem Toxicol 40:1685-92. 2002
    ..These results suggest that the downregulation of CYP1A1 gene expression by o,p'-DDT in Hepa-1c1c7 cells might be an antagonism of the DRE binding potential of the nuclear Ah receptor but is not mediated through the estradiol receptor...
  100. ncbi Role of the aryl hydrocarbon receptor and Cyp1b1 in the antiestrogenic activity of 2,3,7,8-tetrachlorodibenzo-p-dioxin
    Kei Takemoto
    Division of Drug Metabolism, Faculty of Pharmaceutical Sciences, Kanazawa University, Takara machi 13 1, 920 0934 Kanazawa, Japan
    Arch Toxicol 78:309-15. 2004
    ..6+/-30.1 units/g) compared with that in E2-treated mice. This is the first demonstration that Cyp1b1 as well as AhR is involved in the antiestrogenic effects of TCDD...
  101. ncbi The aryl hydrocarbon receptor predisposes hepatocytes to Fas-mediated apoptosis
    Kyung Tae Park
    Department of Pharmacology and Toxicology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555 1031, USA
    Mol Pharmacol 67:612-22. 2005
    ..Moreover, down-regulation of the aryl hydrocarbon receptor nuclear translocator protein in vivo by adenovirus-mediated RNA interference to suppress AhR activity provided wild-type mice partial protection from Jo2-induced lethality...

Research Grants71

  1. MOLECULAR MECHANISMS OF DIOXIN ACTION
    Alvaro Puga; Fiscal Year: 2013
    ....
  2. Novel Zebrafish Models to Study Toxicity of PCBs and Pesticides During Pregnancy
    Lisa Satterwhite; Fiscal Year: 2009
    ....
  3. Aryl Hydrocarbon Receptor Modulators for the Treatment of Hepatocellular Carcinom
    Siva Kumar Kolluri; Fiscal Year: 2012
    ..We will evaluate some of short-listed SAhRMs for AhR-dependent inhibition of tumor growth in mouse xenografts tumor studies in the future. ..
  4. THE EFFECT OF DIOXINS ON GLUCOSE HOMEOSTASIS IN MURINE TESTES
    KENAN RIFAT OMURTAG; Fiscal Year: 2013
    ..This research will help us better understand how such environmental exposures may affect the male reproductive tract. ..
  5. Role of natural indoles in experimental autoimmune encephalomyelitis
    Mitzi Nagarkatti; Fiscal Year: 2013
    ..These studies should provide novel insights into the basic mechanisms through which plant indoles exhibit anti- inflammatory properties so that they can be used against a wide range of autoimmune and inflammatory diseases. ..
  6. Roles of pulmonary and hepatic P4501A enzymes in hyperoxic lung injury in mice
    Bhagavatula Moorthy; Fiscal Year: 2010
    ..The long-term of this proposal is to develop rational strategies for the prevention and/or treatment of chronic lung diseases in infants and adults suffering from respiratory distress and lung dysfunction. ..
  7. Mucosal Immunity and Microbiota in Intestinal Graft-versus-Host Disease
    Marcel R m van den Brink; Fiscal Year: 2013
    ..Therefore, we expect that these preclinical studies have a high likelihood to improve prophylaxis and treatment of intestinal GVHD as well as overall outcome in allo BMT patients. ..
  8. Modulation of Neonatal Hyperoxic Lung Injury by the Aryl Hydrocarbon Receptor
    Binoy Shivanna; Fiscal Year: 2013
    ..I anticipate that the results will support my hypotheses, which will lead to novel strategies in the prevention and treatment of BPD in premature infants. ..
  9. Paternal Environmental Exposures and Reproductive Outcomes: A Comparison of in Vi
    DEBORAH ANN HANSEN; Fiscal Year: 2013
    ..In vivo and in vitro parameters include: a) 14.5 dpc placental and fetal weights, and crown to rump lengths;b) full term litter size, birth weights, and 5 week growth rates;and c) gross and microscopic structure. ..
  10. Transcription Factor Cross-Talk in Developmental Toxicity
    LARISSA WILLIAMS; Fiscal Year: 2012
    ....
  11. Role of the Aryl Hydrocarbon Receptor in Lung Inflammation
    PATRICIA JANET SIME; Fiscal Year: 2012
    ..Our studies will determine the mechanisms by which the AhR acts to dampen lung inflammation. This new knowledge can be exploited to develop new treatments for patients with lung inflammatory diseases. ..
  12. Cellular Determinants of Ah Receptor Signaling
    Thomas R Sutter; Fiscal Year: 2013
    ..The results of these studies will generate the knowledge that is necessary to design minimally invasive studies using small skin biopsies and tape stripping methods in future translational studies of human populations exposed to dioxin. ..
  13. Xenobiotic sensors PXR and CAR and regulation of the UGT1 locus
    Robert H Tukey; Fiscal Year: 2012
    ..This application is the first attempt to investigate how human UGTs are regulated in mice, and to apply this animal to understand the impact of glucuronidation towards drug-drug interactions, drug metabolism and eventually disease. ..
  14. MECHANISMS OF THE INDUCTION OF ORAL TOLERANCE
    Howard L Weiner; Fiscal Year: 2013
    ..We will investigate mechanisms to induce regulatory T cells by oral tolerance, which takes advantage of natural protective mechanisms that exist in the gut. ..
  15. Low-affinity aryl hydrocarbon receptors in the frog Xenopus laevis
    Wade H Powell; Fiscal Year: 2010
    ..It will also aid in the understanding of important differences between frogs and humans as they interpret toxicology studies using frog embryos as a model system for measuring the effects of chemicals and environmental samples. ..
  16. Impact of aryl hydrocarbon receptor ligand ingestion on gastrointestinal immunity
    Barbara Platzer; Fiscal Year: 2013
    ..Findings of this project could also provide a basis to develop therapeutic strategies to prevent and/or treat food allergic responses through inhibition of AhR activation via natural or chemical AhR antagonists. ..
  17. Ah Receptor and Endothelin-Dependent Hypertension
    Mary K Walker; Fiscal Year: 2010
    ..Our results will define a novel regulatory pathway for suppression of hypoxia-induced ET- 1, which could be use to develop new therapies for ET-1-dependent cardiovascular diseases. ..
  18. Aldo-Keto Reductases and PAH Metabolism/Activation
    Trevor M Penning; Fiscal Year: 2013
    ..These studies will inform genotyping and validate genomic studies of cancer of the airway and improve risk assessment prediction. ..
  19. Genetic Susceptibility to PCB-induced Motor Dysfunction
    CHRISTINE PERDAN CURRAN; Fiscal Year: 2012
    ..The proposed research is designed to identify neural pathways affected by PCB exposure and humans at highest risk of PCB developmental neurotoxicity using a mouse model that mirrors known genetic variations in humans. ..
  20. P53-dependent responses to toxicants in parous and nulliparous breast
    D Joseph Jerry; Fiscal Year: 2010
    ....
  21. Ah Receptor Anatomy: Implications for Dioxin Toxicity
    CORNELIS JOHAN ELFERINK; Fiscal Year: 2011
    ..Parallels between humans and mice in the re- generative response, instills confidence that findings generated during these studies will be directly applicable to the human condition. ..
  22. INNATE AND ADAPTIVE IMMUNITY IN IBD
    Charles O Elson; Fiscal Year: 2013
    ..The long-term goal is to increase our understanding of the fundamental mechanisms of IBD in order to develop better diagnostic and therapeutic strategies for patients...
  23. PPAR-gamma Signaling in Normal Pilosebaceous Units and in Scarring Alopecia
    Pratima Karnik; Fiscal Year: 2013
    ..PHS 398/2590 (Rev. 11/07) Page Continuation Format Page ..
  24. A Novel Role of the Aryl Hydrocarbon Receptor in Hepatic Steatosis
    Wen Xie; Fiscal Year: 2013
    ..It is hoped that results from this study may help to establish AhR as a novel therapeutic target for fatty liver in human patients. ..
  25. AhR activation in Th17 and Treg cell differentiation
    Liang Zhou; Fiscal Year: 2013
    ..Understanding the differentiation of Th17 and Treg cells at molecular levels will shed light on the disease pathogenesis and may eventually provide novel means for treating human infectious and autoimmune diseases. ..
  26. AHR signaling in Mammalian and Non-Mammalian Models
    Mark E Hahn; Fiscal Year: 2013
    ....
  27. Transgenerational exposures as modifiers of host defense against infection
    B Paige Lawrence; Fiscal Year: 2013
    ....
  28. Lymphoid Tissue Inducer/NK22 Cells and Post-transplant Immune Recovery
    Michael R Verneris; Fiscal Year: 2013
    ....
  29. Developmental Ah receptor Activity in the CNS: Neurogenesis and Neurotoxicity
    Lisa A Opanashuk; Fiscal Year: 2013
    ..Moreover, the observations from these studies will offer insight into the cognitive and motor impairments that arise following exposure to dioxin, which is a widespread environmental contaminant. ..
  30. Th1 and Th17 Mediators in Experimental Emphysema
    Farrah Kheradmand; Fiscal Year: 2013
    ..This application captures some of the critical initiation events in smoke-induced inflammation and applies this knowledge to explore new therapeutic options in emphysema. ..
  31. Ah receptor transcriptional regulation through a novel DNA binding site
    SHELLY RENEE WILSON; Fiscal Year: 2012
    ..abstract_text> ..
  32. Aryl Hydrocarbon Receptor Ligands and Thyroid Eye Disease
    Richard P Phipps; Fiscal Year: 2013
    ....
  33. REPRODUCTIVE AND DEVELOPMENTAL TOXICITY OF DIOXIN
    RICHARD EUGENE PETERSON; Fiscal Year: 2013
    ..In addition, it includes the first controlled animal study of whether TCDD exposure in adulthood increases the risk of prostate adenocarcinoma, the most common type of prostate cancer in men. ..
  34. Antagonism of the Ah Receptor in Controlling Breast Cancer Growth and Invasion
    Jennifer J Schlezinger; Fiscal Year: 2010
    ....
  35. The Role of the Aryl Hydrocarbon Receptor in Intestinal Immunity
    Liang Zhou; Fiscal Year: 2012
    ..A better understanding of the role of AhR in the immune system may eventually provide novel means for treating human infectious and autoimmune diseases. ..
  36. TCDD- INDUCED CARDIOTOXICITY IN DEVELOPING ZEBRAFISH
    WARREN NO MIDDLE NAME HEIDEMAN; Fiscal Year: 2013
    ....
  37. Selective Ah Receptor Ligands Repress Acute-Phase Response
    Gary H Perdew; Fiscal Year: 2013
    ..These studies taken together will allow future testing on their therapeutic potential in appropriate chronic inflammatory disease animal models (e.g. cancer, Crohn's disease). ..
  38. Role of Aryl hydrocarbon receptor (AhR) and RelB during the initiation of dendrit
    Christoph F A Vogel; Fiscal Year: 2010
    ..This work will help to understand the mechanism how environmental toxicants like dioxin or dioxin-like compounds, which activate the AhR, elicit immunotoxic effects and lead to adverse health effects. ..
  39. Circadian Clock Disruption: A Mechanism for Dioxin-induced Metabolic Syndrome
    Shelley A Tischkau; Fiscal Year: 2013
    ..This proposal examines the novel hypothesis that dioxins exert their action through aryl hydrocarbon receptor-mediated uncoupling of homeostatic regulation of organismic circadian rhythms. ..
  40. Impact of proximal promoter polymorphisms on AHR gene expression in human lung
    David C Spink; Fiscal Year: 2013
    ..These studies will determine the importance of novel polymorphisms in the AHR gene promoter on AhR expression and may ultimately lead to a clearer understanding of the genetic susceptibility to lung cancer. ..
  41. 3'alpha enhancer regulation by AhR and NF-kappaB/Rel proteins
    COURTNEY ELIZABETH WILLIAMS SULENTIC; Fiscal Year: 2011
    ..Results of these studies will also be applicable to the hazard evaluation of other AhR agonists (and antagonists) which include a wide array of chemicals from environmental, dietary and pharmaceutical origin. ..
  42. Ah Receptor Dysregulation Alters Hematopoietic Stem Cells
    Thomas A Gasiewicz; Fiscal Year: 2013
    ..Furthermore, these events are intimately tied with the process of aging and a variety of diseases, including cancer, whose incidence increases with age. ..
  43. The AHR as a Novel Pathway to the Induction of Regulatory T cells
    Nancy I Kerkvliet; Fiscal Year: 2013
    ....
  44. ANALYSIS OF AH RECEPTOR LIGAND BINDING SPECIFICITY
    Michael Steven Denison; Fiscal Year: 2013
    ..In addition, they will yield insights into the molecular mechanisms of ligand-dependent AhR transformation, the influence of ligand structure on these processes and the diversity of AhR responsiveness. ..
  45. SkyScan 1076 In Vivo Micro-Computed Tomography System
    Timothy M Ryan; Fiscal Year: 2010
    ..The new imaging system will allow more accurate and powerful analyses to be conducted which will help improve diagnosis and treatment of these and other important health issues. ..
  46. Role of aryl hydrocarbon receptor in IL-10 producing Tr1 regulatory cells
    Francisco J Quintana; Fiscal Year: 2013
    ..We will investigate how a protein called Aryl Hydrocarbon Receptor controls the immune system and how affecting it ameliorates an animal model of multiple sclerosis. ..
  47. Transcriptional Control of Autoimmunity in the Central Nervous System
    Howard L Weiner; Fiscal Year: 2013
    ..The core will service all projects. An Administrative Core will coordinate the various administrative aspects of the PPG and a Scientific Advisory Board has been assembled to provide scientific oversight. ..
  48. Mechanisms of Herpetic Keratitis
    Barry T Rouse; Fiscal Year: 2013
    ..We shall also use drugs that activate aryl hydrocarbon receptors expressed by activated T cells, which should inhibit the inflammatory activity of such cells as well as ..
  49. Effect of Resveratrol on Staphylococcal Enterotoxin B induced Vascular Leak
    SADIYE AMCAOGLU RIEDER; Fiscal Year: 2010
    ....
  50. Mechanisms of Reduced Heart Failure Pathogenesis with Phytochemical Intake
    Steven F Bolling; Fiscal Year: 2012
    ..In addition, our comparative studies may suggest classes of phytochemicals that provide superior cardioprotection. ..
  51. Impaired B cell Activation/Differentiation via Sustained BCL6 Expression by TCDD
    Norbert E Kaminski; Fiscal Year: 2013
    ..Finally, the proposed experiments will provide new knowledge concerning the fundamental role of the AHR in B cell immunobiology. ..
  52. REGULATION OF THE AH RECEPTOR
    Gary H Perdew; Fiscal Year: 2013
    ..The attenuation of cholesterol synthesis through the use of SAhRM has the potential to impact a variety of diseases, such as atherosclerosis and nonalcoholic fatty liver disease. ..
  53. Role of AhR During Megakaryopoiesis
    STEPHAN CADET LINDSEY; Fiscal Year: 2011
    ....
  54. Modulating AhR in tumor and lymphoid microenvironments via local drug delivery
    GREGORY SZETO; Fiscal Year: 2013
    ..This study will have broad impact in the fields of cancer biology and therapy, immunology, and AhR biology. ..
  55. Glucose Transport in Regulation of T Cell Activation and Inflammation
    Jeffrey C Rathmell; Fiscal Year: 2012
    ....
  56. PCBs: Environmental Modulators of Human Breast Cancer Progression
    MELISSA A RUNGE MORRIS; Fiscal Year: 2010
    ..These studies will employ a unique model of human breast cancer progression to shed new light on the core mechanisms by which environmental PCBs promote cancer development. ..
  57. Transcriptional regulation of polycyclic aromatic hydrocarbon metabolism
    Jeffrey M Peters; Fiscal Year: 2013
    ..In these studies, we will examine new proteins that may interact with AHR signaling and identify novel pathways that may modulate chemically- induced toxicity and cancers. ..
  58. The Role of the Aryl Hy drocarbon Receptor in the Ovary
    Jodi A Flaws; Fiscal Year: 2010
    ..In turn, this improved understanding may lead to the development of novel targets for the treatment and/or prevention of infertility. ..
  59. The Aryl Hydrocarbon Receptor and Breast Cancer
    Sakina E Eltom; Fiscal Year: 2013
    ..Our findings may validate the AhR as a new predictive clinical marker and a unique target for designing novel selective inhibitors for therapeutic intervention of metastatic breast cancer. ..
  60. Transgenic Models of Ah Receptor Action
    Christopher A Bradfield; Fiscal Year: 2013
    ..Collectively these studies will set the stage for more accurate and informative risk assessment in man. ..
  61. Genetic Insight Into AH Receptor-Mediated Promotion Of Hepatocarcinogenesis
    GREGORY DEAN KENNEDY; Fiscal Year: 2013
    ..Specific Aim 3: Examine existing candidate genes for roles upstream of AHR-mediated tumor promotion. Specific Aim 4: Identify additional genes that are candidates for roles in AHR-mediated tumor promotion. ..
  62. Use of Resveratrol to treat experimental multiple sclerosis
    Prakash S Nagarkatti; Fiscal Year: 2011
    ..Together, our studies should provide novel mechanistic clues on how RES helps in the treatment of MS and develop better CAM therapies to control the disease...
  63. Mechanisms of Aryl-Hydrocarbon-Induced Ovotoxicity
    Jonathan Tilly; Fiscal Year: 2005
    ....
  64. Aryl hydrocarbon receptor regulation of the cell cycle by chromatin modification
    REBEKA MERSON; Fiscal Year: 2009
    ..Furthermore, the results will provide the basic research for developing therapeutic interventions to chemical-induced tumors and may predict cell cycle stages susceptible to cancer. ..
  65. REGULATION OF NA,K ATPASE BY THE AH RECEPTOR
    Mary Walker; Fiscal Year: 2004
    ..Selmin, University of Arizona, by PCR-selected subtractive hybridization method and screening of gene microarrays. ..
  66. CHARACTERIZATION OF AH RECEPTOR-RADIOLIGAND INTERACTIONS
    Stephen Safe; Fiscal Year: 1991
    ....
  67. ARNT ISOFORMS FROM ONCORHYNCHUS MYKISS
    RICHARD POLLENZ; Fiscal Year: 2002
    ..Additionally, a detailed study of the function, expression and regulation of ARNT has not been completed in any species. ..
  68. ENDOGENOUS CYP1B1 SUBSTRATES AS AHR LIGANDS
    Craig Marcus; Fiscal Year: 2003
    ..abstract_text> ..
  69. PROMOTION OF HEPATIC NEOPLASIA BY PCB MIXTURES
    Charles Dean; Fiscal Year: 2002
    ..He will be mentored by a faculty committee with research expertise in toxicology, pathology, molecular biology, and carcinogenesis. ..
  70. Ah receptor-mediated deregulation of lactogenesis
    B Paige Lawrence; Fiscal Year: 2009
    ....
  71. AhR-mediated enhancement of the early innate immune response to S. pneumoniae
    BETH VORDERSTRASSE; Fiscal Year: 2009
    ..It is our goal to understand the mechanism of this protection, in hopes that this information can be used to improve current therapies for pneumococcal diseases. ..