Transgenic Overexpression of Aryl Hydrocarbon Receptor Repressor (AhRR) and AhR-Mediated Induction of CYP1A1, Cytokines, and Acute Toxicity.

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  • Additional Information
    • Abstract:
      BACKGROUND: The aryl hydrocarbon receptor repressor (AhRR) is known to repress aryl hydrocarbon receptor (AhR) signaling, but very little is known regarding the role of the AhRR in vivo. OBJECTIVE: This study tested the role of AhRR in vivo in AhRR overexpressing mice on molecular and toxic end points mediated through a prototypical AhR ligand. METHODS: We generated AhRR-transgenic mice (AhRR Tg) based on the genetic background of C57BL/6J wild type (wt) mice. We tested the effect of the prototypical AhR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the expression of cytochrome P450 (CYP)1A1 and cytokines in various tissues of mice. We next analyzed the infiltration of immune cells in adipose tissue of mice after treatment with TCDD using flow cytometry. RESULTS: AhRR Tg mice express significantly higher levels of AhRR compared to wt mice. Activation of AhR by TCDD caused a significant increase of the inflammatory cytokines Interleukin (IL)-1β, IL-6 and IL-10, and CXCL chemokines in white epididymal adipose tissue from both wt and AhRR Tg mice. However, the expression of IL-1β, CXCL2 and CXCL3 were significantly lower in AhRR Tg versus wt mice following TCDD treatment. Exposure to TCDD caused a rapid accumulation of neutrophils and macrophages in white adipose tissue of wt and AhRR Tg mice. Furthermore we found that male AhRR Tg mice were protected from high-dose TCDD-induced lethality associated with a reduced inflammatory response and liver damage as indicated by lower levels of TCDD-induced alanine aminotransferase and hepatic triglycerides. Females from both wt and AhRR Tg mice were less sensitive than male mice to acute toxicity induced by TCDD. CONCLUSION: In conclusion, the current study identifies AhRR as a previously uncharacterized regulator of specific inflammatory cytokines, which may protect from acute toxicity induced by TCDD. [ABSTRACT FROM AUTHOR]
    • Abstract:
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    • Author Affiliations:
      1Department of Environmental Toxicology, University of California, Davis, Davis, California, USA
      2Center for Health and the Environment, University of California, Davis, Davis, California, USA
      3Center for Comparative Medicine, University of California, Davis, Davis, California, USA
      4Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany
      5Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, Davis, California, USA
    • Full Text Word Count:
      10733
    • ISSN:
      0091-6765
    • Accession Number:
      10.1289/ehp.1510194
    • Accession Number:
      116593397
  • Citations
    • ABNT:
      VOGEL, C. F. A. et al. Transgenic Overexpression of Aryl Hydrocarbon Receptor Repressor (AhRR) and AhR-Mediated Induction of CYP1A1, Cytokines, and Acute Toxicity. Environmental Health Perspectives, [s. l.], v. 124, n. 7, p. 1071–1083, 2016. DOI 10.1289/ehp.1510194. Disponível em: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=8gh&AN=116593397. Acesso em: 21 out. 2020.
    • AMA:
      Vogel CFA, Chang WLW, Kado S, et al. Transgenic Overexpression of Aryl Hydrocarbon Receptor Repressor (AhRR) and AhR-Mediated Induction of CYP1A1, Cytokines, and Acute Toxicity. Environmental Health Perspectives. 2016;124(7):1071-1083. doi:10.1289/ehp.1510194
    • APA:
      Vogel, C. F. A., Chang, W. L. W., Kado, S., McCulloh, K., Vogel, H., Wu, D., Haarmann-Stemmann, T., GuoXiang Yang, Leung, P. S. C., Matsumura, F., & Gershwin, M. E. (2016). Transgenic Overexpression of Aryl Hydrocarbon Receptor Repressor (AhRR) and AhR-Mediated Induction of CYP1A1, Cytokines, and Acute Toxicity. Environmental Health Perspectives, 124(7), 1071–1083. https://doi.org/10.1289/ehp.1510194
    • Chicago/Turabian: Author-Date:
      Vogel, Christoph F. A., W. L. William Chang, Sarah Kado, Kelly McCulloh, Helena Vogel, Dalei Wu, Thomas Haarmann-Stemmann, et al. 2016. “Transgenic Overexpression of Aryl Hydrocarbon Receptor Repressor (AhRR) and AhR-Mediated Induction of CYP1A1, Cytokines, and Acute Toxicity.” Environmental Health Perspectives 124 (7): 1071–83. doi:10.1289/ehp.1510194.
    • Harvard:
      Vogel, C. F. A. et al. (2016) ‘Transgenic Overexpression of Aryl Hydrocarbon Receptor Repressor (AhRR) and AhR-Mediated Induction of CYP1A1, Cytokines, and Acute Toxicity’, Environmental Health Perspectives, 124(7), pp. 1071–1083. doi: 10.1289/ehp.1510194.
    • Harvard: Australian:
      Vogel, CFA, Chang, WLW, Kado, S, McCulloh, K, Vogel, H, Wu, D, Haarmann-Stemmann, T, GuoXiang Yang, Leung, PSC, Matsumura, F & Gershwin, ME 2016, ‘Transgenic Overexpression of Aryl Hydrocarbon Receptor Repressor (AhRR) and AhR-Mediated Induction of CYP1A1, Cytokines, and Acute Toxicity’, Environmental Health Perspectives, vol. 124, no. 7, pp. 1071–1083, viewed 21 October 2020, .
    • MLA:
      Vogel, Christoph F. A., et al. “Transgenic Overexpression of Aryl Hydrocarbon Receptor Repressor (AhRR) and AhR-Mediated Induction of CYP1A1, Cytokines, and Acute Toxicity.” Environmental Health Perspectives, vol. 124, no. 7, July 2016, pp. 1071–1083. EBSCOhost, doi:10.1289/ehp.1510194.
    • Chicago/Turabian: Humanities:
      Vogel, Christoph F. A., W. L. William Chang, Sarah Kado, Kelly McCulloh, Helena Vogel, Dalei Wu, Thomas Haarmann-Stemmann, et al. “Transgenic Overexpression of Aryl Hydrocarbon Receptor Repressor (AhRR) and AhR-Mediated Induction of CYP1A1, Cytokines, and Acute Toxicity.” Environmental Health Perspectives 124, no. 7 (July 2016): 1071–83. doi:10.1289/ehp.1510194.
    • Vancouver/ICMJE:
      Vogel CFA, Chang WLW, Kado S, McCulloh K, Vogel H, Wu D, et al. Transgenic Overexpression of Aryl Hydrocarbon Receptor Repressor (AhRR) and AhR-Mediated Induction of CYP1A1, Cytokines, and Acute Toxicity. Environmental Health Perspectives [Internet]. 2016 Jul [cited 2020 Oct 21];124(7):1071–83. Available from: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=8gh&AN=116593397