Aryl hydrocarbon receptor suppresses TNF-alpha production in macrophages
Kofi
Aryl hydrocarbon receptor in combination with Stat1 regulates
LPS-induced inflammatory responses.
Kimura A, Naka T, Nakahama T, Chinen I, Masuda K, Nohara K,
Fujii-Kuriyama Y, Kishimoto T.
Laboratory of Immune Regulation, Osaka University Graduate School of
Frontier Biosciences, Suita, Osaka 565-0871, Japan.
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.
Publication Types:
* Research Support, Non-U.S. Gov't
PMID: 19703987
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