SOCS1/JAB is a negative regulator of LPS-induced macrophage activation

Ichiko Kinjyo, Toshikatsu Hanada, Kyoko Inagaki-Ohara, Hiroyuki Mori, Daisuke Aki, Masanobu Ohishi, Hiroki Yoshida, Masato Kubo, Akihiko Yoshimura

Research output: Contribution to journalArticle

505 Citations (Scopus)


Bacterial lipopolysaccharide (LPS) triggers innate immune responses through Toll-like receptor (TLR) 4. We show here that the suppressor of cytokine-signaling-1 (SOCS1/JAB) is rapidly induced by LPS and negatively regulates LPS signaling. SOCS1+/- mice or SOCS1-/- mice with interferon-γ (IFNγ)-deficient background were more sensitive to LPS-induced lethal effects than were wild-type littermates. LPS-induced NO2- synthesis and TNFα production were augmented in SOCS1-/- macrophages. Furthermore, LPS tolerance, a protection mechanism against endotoxin shock, was also strikingly reduced in SOCS1-/- cells. LPS-induced I-κB and p38 phosphorylation was upregulated in SOCS1-/- macrophages, and forced expression of SOCS1 suppressed LPS-induced NF-κB activation. Thus, SOCS1 directly suppresses TLR4 signaling and modulates innate immunity.

Original languageEnglish
Pages (from-to)583-591
Number of pages9
Issue number5
Publication statusPublished - 2002 Nov 1
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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  • Cite this

    Kinjyo, I., Hanada, T., Inagaki-Ohara, K., Mori, H., Aki, D., Ohishi, M., Yoshida, H., Kubo, M., & Yoshimura, A. (2002). SOCS1/JAB is a negative regulator of LPS-induced macrophage activation. Immunity, 17(5), 583-591.