期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 102, 期 47, 页码 17089-17094出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0508517102
关键词
innate immunity; JAK2; STAT5; toll-like receptor signal
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-alpha, granulocyte colony-stimulating factor, IFN-beta, 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 LIPS signaling by regulating JAK-STAT.
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