Aryl hydrocarbon receptor in combination with Stat1 regulates LPS-induced inflammatory responses

Akihiro Kimura, Tetsuji Naka, Taisuke Nakahama, Ichino Chinen, Kazuya Masuda, Keiko Nohara, Yoshiaki Fujii-Kuriyama, Tadamitsu Kishimoto

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

Original languageEnglish
Pages (from-to)2027-2035
Number of pages9
JournalJournal of Experimental Medicine
Volume206
Issue number9
DOIs
Publication statusPublished - 2009 Aug 31

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

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. Journal of Experimental Medicine, 206(9), 2027-2035. https://doi.org/10.1084/jem.20090560