title: Aryl hydrocarbon receptor in combination with Stat1 regulates LPS-induced inflammatory responses.
abstract: Toll-like receptor (TLR) signals perform a crucial role in innate immune responses to pathogens. In this study, we found that the aryl hydrocarbon receptor (Ahr) negatively regulates inflammatory responses mediated by lipopolysaccharide (LPS) in macrophages. Ahr was induced in macrophages stimulated by LPS, but not by transforming growth factor (TGF)-beta plus interleukin (IL)-6, which can induce Ahr in naive T cells. The production of IL-6 and tumor necrosis factor (TNF)-alpha by LPS was significantly elevated in Ahr-deficient macrophages compared with that in wild-type (WT) cells. Ahr-deficient mice were more highly sensitive to LPS-induced lethal shock than WT mice. Signal transducer and activator of transcription 1 (Stat1) deficiency, as well as Ahr deficiency, augmented LPS-induced IL-6 production. We found that Ahr forms a complex with Stat1 and nuclear factor-kappa B (NF-kappaB) in macrophages stimulated by LPS, which leads to inhibition of the promoter activity of IL-6. Ahr thus plays an essential role in the negative regulation of the LPS signaling pathway through interaction with Stat1.
authors.affiliation: Laboratory of Immune Regulation, Osaka University Graduate School of Frontier Biosciences, Suita, Osaka 565-0871, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kimura
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Naka
authors.forename: Taisuke
authors.initials: T
authors.lastname: Nakahama
authors.forename: Ichino
authors.initials: I
authors.lastname: Chinen
authors.forename: Kazuya
authors.initials: K
authors.lastname: Masuda
authors.forename: Keiko
authors.initials: K
authors.lastname: Nohara
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Fujii-Kuriyama
authors.forename: Tadamitsu
authors.initials: T
authors.lastname: Kishimoto
mesh_terms: D000818:Animals; D015153:Blotting, Western; D047369:Chromatin Immunoprecipitation; D017931:DNA Primers / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000276:immunology*; D047468:Immunoprecipitation; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides; D008156:Luciferases; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D046912:Multiprotein Complexes / Q000276:immunology* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000276:immunology* / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D017931:DNA Primers; D015850:Interleukin-6; D008070:Lipopolysaccharides; D046912:Multiprotein Complexes; D016328:NF-kappa B; D018336:Receptors, Aryl Hydrocarbon; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D008156:Luciferases
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