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¹ Laboratory of Immune Regulation, Osaka University Graduate School of Frontier Biosciences, Suita, Osaka 565-0871, Japan
² Laboratory for Immune Signal, National Institute of Biomedical Innovation, Ibaraki City, Osaka 567-0085, Japan
³ Environmental Health Sciences Division, National Institute for Environmental Studies, Tsukuba, Ibaraki 305-8506, Japan
⁴ Center for Tsukuba Advanced Research Alliance and Institute of Basic Medical Sciences, University of Tsukuba, 1-1-1, Tennoudai, Tsukuba 305-8577, Japan

CORRESPONDENCE Tadamitsu Kishimoto: kishimot{at}imed3.med.osaka-u.ac.jp

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)-β plus interleukin (IL)-6, which can induce Ahr in naive T cells. The production of IL-6 and tumor necrosis factor (TNF)- 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-B) 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.

© 2009 Kimura et al.
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This article has been cited by other articles:

• Kimura, A., Naka, T., Nakahama, T., Chinen, I., Masuda, K., Nohara, K., Fujii-Kuriyama, Y., Kishimoto, T. (2009). Aryl hydrocarbon receptor in combination with Stat1 regulates LPS-induced inflammatory responses. JCB 186: i8-i8 [Full Text]  

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