IL-6 induces an anti-inflammatory response in the absence of SOCS3 in macrophages

Hideo Yasukawa, Masanobu Ohishi, Hiroyuki Mori, Masaaki Murakami, Takatoshi Chinen, Daisuke Aki, Toshikatsu Hanada, Kiyoshi Takeda, Shizuo Akira, Masahiko Hoshijima, Toshio Hirano, Kenneth R. Chien, Akihiko Yoshimura

Research output: Contribution to journalArticle

531 Citations (Scopus)

Abstract

Whereas interleukin-6 (IL-6) is a proinflammatory cytokine, IL-10 is an anti-inflammatory cytokine. Although signal transducer and activator of transcription 3 (STAT3) is essential for the function of both IL-6 and IL-10, it is unclear how these two cytokines have such opposing functions. Here we show that suppressor of cytokine signaling 3 (SOCS3) is a key regulator of the divergent action of these two cytokines. In macrophages lacking the Socs3 gene or carrying a mutation of the SOCS3-binding site in gp130, the lipopolysaccharide-induced production of tumor necrosis factor (TNF) and IL-12 is suppressed by both IL-10 and IL-6. SOCS3 specifically prevents activation of STAT3 by IL-6 but not IL-10. Taken together, these data indicate that SOCS3 selectively blocks signaling by IL-6, thereby preventing its ability to inhibit LPS signaling.

Original languageEnglish
Pages (from-to)551-556
Number of pages6
JournalNature Immunology
Volume4
Issue number6
DOIs
Publication statusPublished - 2003 Jun 1
Externally publishedYes

Fingerprint

Interleukin-6
Anti-Inflammatory Agents
Macrophages
Cytokines
Interleukin-10
STAT3 Transcription Factor
Genetic Suppression
Interleukin-12
Lipopolysaccharides
Tumor Necrosis Factor-alpha
Binding Sites
Genes

ASJC Scopus subject areas

  • Immunology

Cite this

IL-6 induces an anti-inflammatory response in the absence of SOCS3 in macrophages. / Yasukawa, Hideo; Ohishi, Masanobu; Mori, Hiroyuki; Murakami, Masaaki; Chinen, Takatoshi; Aki, Daisuke; Hanada, Toshikatsu; Takeda, Kiyoshi; Akira, Shizuo; Hoshijima, Masahiko; Hirano, Toshio; Chien, Kenneth R.; Yoshimura, Akihiko.

In: Nature Immunology, Vol. 4, No. 6, 01.06.2003, p. 551-556.

Research output: Contribution to journalArticle

Yasukawa, H, Ohishi, M, Mori, H, Murakami, M, Chinen, T, Aki, D, Hanada, T, Takeda, K, Akira, S, Hoshijima, M, Hirano, T, Chien, KR & Yoshimura, A 2003, 'IL-6 induces an anti-inflammatory response in the absence of SOCS3 in macrophages', Nature Immunology, vol. 4, no. 6, pp. 551-556. https://doi.org/10.1038/ni938
Yasukawa, Hideo ; Ohishi, Masanobu ; Mori, Hiroyuki ; Murakami, Masaaki ; Chinen, Takatoshi ; Aki, Daisuke ; Hanada, Toshikatsu ; Takeda, Kiyoshi ; Akira, Shizuo ; Hoshijima, Masahiko ; Hirano, Toshio ; Chien, Kenneth R. ; Yoshimura, Akihiko. / IL-6 induces an anti-inflammatory response in the absence of SOCS3 in macrophages. In: Nature Immunology. 2003 ; Vol. 4, No. 6. pp. 551-556.
@article{1a80d78b96b347d5bed2b7e05c798980,
title = "IL-6 induces an anti-inflammatory response in the absence of SOCS3 in macrophages",
abstract = "Whereas interleukin-6 (IL-6) is a proinflammatory cytokine, IL-10 is an anti-inflammatory cytokine. Although signal transducer and activator of transcription 3 (STAT3) is essential for the function of both IL-6 and IL-10, it is unclear how these two cytokines have such opposing functions. Here we show that suppressor of cytokine signaling 3 (SOCS3) is a key regulator of the divergent action of these two cytokines. In macrophages lacking the Socs3 gene or carrying a mutation of the SOCS3-binding site in gp130, the lipopolysaccharide-induced production of tumor necrosis factor (TNF) and IL-12 is suppressed by both IL-10 and IL-6. SOCS3 specifically prevents activation of STAT3 by IL-6 but not IL-10. Taken together, these data indicate that SOCS3 selectively blocks signaling by IL-6, thereby preventing its ability to inhibit LPS signaling.",
author = "Hideo Yasukawa and Masanobu Ohishi and Hiroyuki Mori and Masaaki Murakami and Takatoshi Chinen and Daisuke Aki and Toshikatsu Hanada and Kiyoshi Takeda and Shizuo Akira and Masahiko Hoshijima and Toshio Hirano and Chien, {Kenneth R.} and Akihiko Yoshimura",
year = "2003",
month = "6",
day = "1",
doi = "10.1038/ni938",
language = "English",
volume = "4",
pages = "551--556",
journal = "Nature Immunology",
issn = "1529-2908",
publisher = "Nature Publishing Group",
number = "6",

}

TY - JOUR

T1 - IL-6 induces an anti-inflammatory response in the absence of SOCS3 in macrophages

AU - Yasukawa, Hideo

AU - Ohishi, Masanobu

AU - Mori, Hiroyuki

AU - Murakami, Masaaki

AU - Chinen, Takatoshi

AU - Aki, Daisuke

AU - Hanada, Toshikatsu

AU - Takeda, Kiyoshi

AU - Akira, Shizuo

AU - Hoshijima, Masahiko

AU - Hirano, Toshio

AU - Chien, Kenneth R.

AU - Yoshimura, Akihiko

PY - 2003/6/1

Y1 - 2003/6/1

N2 - Whereas interleukin-6 (IL-6) is a proinflammatory cytokine, IL-10 is an anti-inflammatory cytokine. Although signal transducer and activator of transcription 3 (STAT3) is essential for the function of both IL-6 and IL-10, it is unclear how these two cytokines have such opposing functions. Here we show that suppressor of cytokine signaling 3 (SOCS3) is a key regulator of the divergent action of these two cytokines. In macrophages lacking the Socs3 gene or carrying a mutation of the SOCS3-binding site in gp130, the lipopolysaccharide-induced production of tumor necrosis factor (TNF) and IL-12 is suppressed by both IL-10 and IL-6. SOCS3 specifically prevents activation of STAT3 by IL-6 but not IL-10. Taken together, these data indicate that SOCS3 selectively blocks signaling by IL-6, thereby preventing its ability to inhibit LPS signaling.

AB - Whereas interleukin-6 (IL-6) is a proinflammatory cytokine, IL-10 is an anti-inflammatory cytokine. Although signal transducer and activator of transcription 3 (STAT3) is essential for the function of both IL-6 and IL-10, it is unclear how these two cytokines have such opposing functions. Here we show that suppressor of cytokine signaling 3 (SOCS3) is a key regulator of the divergent action of these two cytokines. In macrophages lacking the Socs3 gene or carrying a mutation of the SOCS3-binding site in gp130, the lipopolysaccharide-induced production of tumor necrosis factor (TNF) and IL-12 is suppressed by both IL-10 and IL-6. SOCS3 specifically prevents activation of STAT3 by IL-6 but not IL-10. Taken together, these data indicate that SOCS3 selectively blocks signaling by IL-6, thereby preventing its ability to inhibit LPS signaling.

UR - http://www.scopus.com/inward/record.url?scp=0037600741&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037600741&partnerID=8YFLogxK

U2 - 10.1038/ni938

DO - 10.1038/ni938

M3 - Article

VL - 4

SP - 551

EP - 556

JO - Nature Immunology

JF - Nature Immunology

SN - 1529-2908

IS - 6

ER -