In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 102, No. 47 ( 2005-11-22), p. 17089-17094
Abstract:
Suppressor of cytokine signaling-1 (SOCS-1) is one of the negative-feedback regulators of Janus kinase (JAK)–signal transducer and activator of transcription (STAT) signaling. We previously showed that SOCS-1 participates in LPS signaling, but it is not entirely clear yet how SOCS-1 suppresses LPS signaling. In this study, we demonstrate that SOCS-1 selectively inhibits LPS-induced IL-6 production through regulation of JAK–STAT but not production of TNF-α, granulocyte colony-stimulating factor, IFN-β, and other cytokines. We found that LPS directly activated Jak2 and Stat5, whereas SOCS-1 inhibited LPS-induced Jak2 and Stat5 activation. Furthermore, AG490, a Jak-specific inhibitor, and dominant negative Stat5 only reduced LPS-induced IL-6 production. Additionally, Stat5 interacted with p50, resulting in recruitment of Stat5 to the IL-6 promoter together with p50 in response to LPS stimulation. These findings suggest that the JAK–STAT pathway participates in LPS-induced IL-6 production and that SOCS-1 suppresses LPS signaling by regulating JAK–STAT.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.0508517102
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2005
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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