Suppressor of cytokine signaling-1 selectively inhibits LPS-induced IL-6 production by regulating JAK-STAT

Akihiro Kimura, Tetsuji Naka, Tatsushi Muta, Osamu Takeuchi, Shizuo Akira, Ichiro Kawase, Tadamitsu Kishimoto

Research output: Contribution to journalArticle

113 Citations (Scopus)

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-a, granulocyte colony-stimulating factor, IFN-β, and other cytokines. We found that LPS directly activated Jak2 and StatS, whereas SOCS-1 inhibited LPS-induced Jak2 and StatS activation. Further-more, AG490, a Jak-specific inhibitor, and dominant negative StatS only reduced LPS-induced IL-6 production. Additionally, StatS interacted with p50, resulting in recruitment of StatS 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.

Original languageEnglish
Pages (from-to)17089-17094
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number47
DOIs
Publication statusPublished - 2005 Nov 22

Fingerprint

Janus Kinases
Transducers
Interleukin-6
Cytokines
Granulocyte Colony-Stimulating Factor

Keywords

  • Innate immunity
  • Jak2
  • Stat5
  • Toll-like receptor signal

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Suppressor of cytokine signaling-1 selectively inhibits LPS-induced IL-6 production by regulating JAK-STAT. / Kimura, Akihiro; Naka, Tetsuji; Muta, Tatsushi; Takeuchi, Osamu; Akira, Shizuo; Kawase, Ichiro; Kishimoto, Tadamitsu.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 102, No. 47, 22.11.2005, p. 17089-17094.

Research output: Contribution to journalArticle

Kimura, Akihiro ; Naka, Tetsuji ; Muta, Tatsushi ; Takeuchi, Osamu ; Akira, Shizuo ; Kawase, Ichiro ; Kishimoto, Tadamitsu. / Suppressor of cytokine signaling-1 selectively inhibits LPS-induced IL-6 production by regulating JAK-STAT. In: Proceedings of the National Academy of Sciences of the United States of America. 2005 ; Vol. 102, No. 47. pp. 17089-17094.
@article{48c81a8fae02443bbcf445c91d4c5ccc,
title = "Suppressor of cytokine signaling-1 selectively inhibits LPS-induced IL-6 production by regulating JAK-STAT",
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-a, granulocyte colony-stimulating factor, IFN-β, and other cytokines. We found that LPS directly activated Jak2 and StatS, whereas SOCS-1 inhibited LPS-induced Jak2 and StatS activation. Further-more, AG490, a Jak-specific inhibitor, and dominant negative StatS only reduced LPS-induced IL-6 production. Additionally, StatS interacted with p50, resulting in recruitment of StatS 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.",
keywords = "Innate immunity, Jak2, Stat5, Toll-like receptor signal",
author = "Akihiro Kimura and Tetsuji Naka and Tatsushi Muta and Osamu Takeuchi and Shizuo Akira and Ichiro Kawase and Tadamitsu Kishimoto",
year = "2005",
month = "11",
day = "22",
doi = "10.1073/pnas.0508517102",
language = "English",
volume = "102",
pages = "17089--17094",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "47",

}

TY - JOUR

T1 - Suppressor of cytokine signaling-1 selectively inhibits LPS-induced IL-6 production by regulating JAK-STAT

AU - Kimura, Akihiro

AU - Naka, Tetsuji

AU - Muta, Tatsushi

AU - Takeuchi, Osamu

AU - Akira, Shizuo

AU - Kawase, Ichiro

AU - Kishimoto, Tadamitsu

PY - 2005/11/22

Y1 - 2005/11/22

N2 - 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-a, granulocyte colony-stimulating factor, IFN-β, and other cytokines. We found that LPS directly activated Jak2 and StatS, whereas SOCS-1 inhibited LPS-induced Jak2 and StatS activation. Further-more, AG490, a Jak-specific inhibitor, and dominant negative StatS only reduced LPS-induced IL-6 production. Additionally, StatS interacted with p50, resulting in recruitment of StatS 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.

AB - 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-a, granulocyte colony-stimulating factor, IFN-β, and other cytokines. We found that LPS directly activated Jak2 and StatS, whereas SOCS-1 inhibited LPS-induced Jak2 and StatS activation. Further-more, AG490, a Jak-specific inhibitor, and dominant negative StatS only reduced LPS-induced IL-6 production. Additionally, StatS interacted with p50, resulting in recruitment of StatS 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.

KW - Innate immunity

KW - Jak2

KW - Stat5

KW - Toll-like receptor signal

UR - http://www.scopus.com/inward/record.url?scp=28044461950&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=28044461950&partnerID=8YFLogxK

U2 - 10.1073/pnas.0508517102

DO - 10.1073/pnas.0508517102

M3 - Article

C2 - 16287972

AN - SCOPUS:28044461950

VL - 102

SP - 17089

EP - 17094

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 47

ER -