SOCS-1 participates in negative regulation of LPS responses

Reiko Nakagawa, Tetsuji Naka, Hiroko Tsutsui, Minoru Fujimoto, Akihiro Kimura, Tatsuo Abe, Ekihiro Seki, Shintaro Sato, Osamu Takeuchi, Kiyoshi Takeda, Shizuo Akira, Koichi Yamanishi, Ichirou Kawase, Kenji Nakanishi, Tadamitsu Kishimoto

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516 Citations (Scopus)

Abstract

SOCS-1 is a negative regulatory molecule of the JAK-STAT signal cascade. Here, we demonstrate that SOCS-1 is a critical downregulating factor for LPS signal pathways. SOCS-1 expression was promptly induced in macrophages upon LPS stimulation. SOCS-1-deficient mice were highly sensitive to LPS-induced shock and produced increased levels of inflammatory cytokines. Introduction of SOCS-1 inhibited LPS-induced NF-κB and STAT1 activation in macrophages. Furthermore, LPS tolerance, a refractory state to second LPS stimulation, was not observed in SOCS-1-deficient mice. These results suggest SOCS-1 as an essential, negative regulator in LPS responses that protects the host from harmful overresponses to LPS and may provide new insight into the endotoxin-induced fatal syndrome that occasionally occurs following infection.

Original languageEnglish
Pages (from-to)677-687
Number of pages11
JournalImmunity
Volume17
Issue number5
DOIs
Publication statusPublished - 2002 Nov 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Nakagawa, R., Naka, T., Tsutsui, H., Fujimoto, M., Kimura, A., Abe, T., Seki, E., Sato, S., Takeuchi, O., Takeda, K., Akira, S., Yamanishi, K., Kawase, I., Nakanishi, K., & Kishimoto, T. (2002). SOCS-1 participates in negative regulation of LPS responses. Immunity, 17(5), 677-687. https://doi.org/10.1016/S1074-7613(02)00449-1