| 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
|
| Resource |
| Human and Animal Cells |
RAW 264(RCB0535) |
