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

被引：657

作者：

Kinjyo, I

Hanada, T

Inagaki-Ohara, K

Mori, H

Aki, D

Ohishi, M

Yoshida, H

Kubo, M

Yoshimura, A

机构：

[1] Kyushu Univ, Med Inst Bioregulat, Div Mol & Cellular Immunol, Higashi Ku, Fukuoka 8128582, Japan

[2] Tokyo Univ Sci, Div Immunobiol, Res Inst Biol sci, Noda, Chiba 2780022, Japan

来源：

IMMUNITY | 2002年 / 17卷 / 05期

关键词：

D O I：

10.1016/S1074-7613(02)00446-6

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 [免疫学];

摘要：

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 LIPS and negatively regulates LPS signaling. SOCS+/- mice or SOCSi-/- mice with interferon-gamma (IFNgamma)-deficient background were more sensitive to LPS-induced lethal effects than were wild-type littermates. LPS-induced NO2- synthesis and TNFalpha production were augmented in SOCS1(-/-)Imacrophages. Furthermore, LPS tolerance, a protection mechanism against endotoxin shock, was also strikingly reduced in SOCS1(-/-) cells. LPS-induced I-kappaB and p38 phosphorylation was upregulated in SOCS1(-/-) macrophages, and forced expression of SOCS1 suppressed LPS-induced NF-kappaB activation. Thus, SOCS1 directly suppresses TLR4 signaling and modulates innate immunity.

引用

收藏

页码：583 / 591

页数：9

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