First Author | Kinjyo I | Year | 2002 |
Journal | Immunity | Volume | 17 |
Issue | 5 | Pages | 583-91 |
PubMed ID | 12433365 | Mgi Jnum | J:125159 |
Mgi Id | MGI:3757785 | Doi | 10.1016/s1074-7613(02)00446-6 |
Citation | Kinjyo I, et al. (2002) SOCS1/JAB is a negative regulator of LPS-induced macrophage activation. Immunity 17(5):583-91 |
abstractText | 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. |