SOCS-1 Participates in Negative Regulation of LPS Responses
- 作者：Reiko Nakagawa ; Tetsuji Naka ; Hiroko Tsutsui ; Minoru Fujimoto ; Akihiro Kimura ; Tatsuo Abe ; Ekihiro Seki ; Shintaro Sato ; Osamu Takeuchi ; Kiyoshi Takeda et al.
- 刊名：Immunity
- 出版年：2002
- 期刊代码：40_10747613
- 类别：imm
- 出版时间：November 2002
- 卷：17
- 期：5
- 页码：677-687
- 文件大小：436 K
摘要
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.