IL-6 induces an anti-inflammatory response in the absence of SOCS3 in macrophages

Hideo Yasukawa, Masanobu Ohishi, Hiroyuki Mori, Masaaki Murakami, Takatoshi Chinen, Daisuke Aki, Toshikatsu Hanada, Kiyoshi Takeda, Shizuo Akira, Masahiko Hoshijima, Toshio Hirano, Kenneth R. Chien, Akihiko Yoshimura

Research output: Contribution to journalArticle

557 Citations (Scopus)

Abstract

Whereas interleukin-6 (IL-6) is a proinflammatory cytokine, IL-10 is an anti-inflammatory cytokine. Although signal transducer and activator of transcription 3 (STAT3) is essential for the function of both IL-6 and IL-10, it is unclear how these two cytokines have such opposing functions. Here we show that suppressor of cytokine signaling 3 (SOCS3) is a key regulator of the divergent action of these two cytokines. In macrophages lacking the Socs3 gene or carrying a mutation of the SOCS3-binding site in gp130, the lipopolysaccharide-induced production of tumor necrosis factor (TNF) and IL-12 is suppressed by both IL-10 and IL-6. SOCS3 specifically prevents activation of STAT3 by IL-6 but not IL-10. Taken together, these data indicate that SOCS3 selectively blocks signaling by IL-6, thereby preventing its ability to inhibit LPS signaling.

Original languageEnglish
Pages (from-to)551-556
Number of pages6
JournalNature Immunology
Volume4
Issue number6
DOIs
Publication statusPublished - 2003 Jun 1
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Yasukawa, H., Ohishi, M., Mori, H., Murakami, M., Chinen, T., Aki, D., Hanada, T., Takeda, K., Akira, S., Hoshijima, M., Hirano, T., Chien, K. R., & Yoshimura, A. (2003). IL-6 induces an anti-inflammatory response in the absence of SOCS3 in macrophages. Nature Immunology, 4(6), 551-556. https://doi.org/10.1038/ni938