RRC ID 41725
Author Kinjyo I, Hanada T, Inagaki-Ohara K, Mori H, Aki D, Ohishi M, Yoshida H, Kubo M, Yoshimura A.
Title SOCS1/JAB is a negative regulator of LPS-induced macrophage activation.
Journal Immunity
Abstract 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-gamma (IFNgamma)-deficient background were more sensitive to LPS-induced lethal effects than were wild-type littermates. LPS-induced NO(2)(-) synthesis and TNFalpha 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-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.
Volume 17(5)
Pages 583-91
Published 2002-11-1
DOI 10.1016/s1074-7613(02)00446-6
PII S1074-7613(02)00446-6
PMID 12433365
MeSH Animals Carrier Proteins / physiology* Cells, Cultured Drosophila Proteins* Lipopolysaccharides / pharmacology Macrophage Activation / drug effects Macrophage Activation / physiology* Macrophages, Peritoneal / physiology* Membrane Glycoproteins / physiology Mice Mice, Inbred C57BL NF-kappa B / physiology Phosphorylation Receptors, Cell Surface / physiology Repressor Proteins* Signal Transduction / drug effects Signal Transduction / physiology Suppressor of Cytokine Signaling 1 Protein Suppressor of Cytokine Signaling Proteins Toll-Like Receptor 4 Toll-Like Receptors
IF 22.553
Times Cited 490
WOS Category IMMUNOLOGY
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The most frequently cited source Patent(IFI CLAIMS)
Total number of mentions 55
Altmetric score changes over past 6months 0.0
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Human and Animal Cells RAW 264(RCB0535)