SOCS1/JAB is a negative regulator of LPS-induced macrophage activation

Ichiko Kinjyo, Toshikatsu Hanada, Kyoko Inagaki-Ohara, Hiroyuki Mori, Daisuke Aki, Masanobu Ohishi, Hiroki Yoshida, Masato Kubo, Akihiko Yoshimura

Research output: Contribution to journalArticle

502 Citations (Scopus)

Abstract

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-γ (IFNγ)-deficient background were more sensitive to LPS-induced lethal effects than were wild-type littermates. LPS-induced NO2- synthesis and TNFα 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-κB and p38 phosphorylation was upregulated in SOCS1-/- macrophages, and forced expression of SOCS1 suppressed LPS-induced NF-κB activation. Thus, SOCS1 directly suppresses TLR4 signaling and modulates innate immunity.

Original languageEnglish
Pages (from-to)583-591
Number of pages9
JournalImmunity
Volume17
Issue number5
DOIs
Publication statusPublished - 2002 Nov 1
Externally publishedYes

Fingerprint

Macrophage Activation
Lipopolysaccharides
Innate Immunity
Macrophages
Toll-Like Receptor 4
Endotoxins
Interferons
Shock
Phosphorylation
Cytokines

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

SOCS1/JAB is a negative regulator of LPS-induced macrophage activation. / Kinjyo, Ichiko; Hanada, Toshikatsu; Inagaki-Ohara, Kyoko; Mori, Hiroyuki; Aki, Daisuke; Ohishi, Masanobu; Yoshida, Hiroki; Kubo, Masato; Yoshimura, Akihiko.

In: Immunity, Vol. 17, No. 5, 01.11.2002, p. 583-591.

Research output: Contribution to journalArticle

Kinjyo, I, Hanada, T, Inagaki-Ohara, K, Mori, H, Aki, D, Ohishi, M, Yoshida, H, Kubo, M & Yoshimura, A 2002, 'SOCS1/JAB is a negative regulator of LPS-induced macrophage activation', Immunity, vol. 17, no. 5, pp. 583-591. https://doi.org/10.1016/S1074-7613(02)00446-6
Kinjyo I, Hanada T, Inagaki-Ohara K, Mori H, Aki D, Ohishi M et al. SOCS1/JAB is a negative regulator of LPS-induced macrophage activation. Immunity. 2002 Nov 1;17(5):583-591. https://doi.org/10.1016/S1074-7613(02)00446-6
Kinjyo, Ichiko ; Hanada, Toshikatsu ; Inagaki-Ohara, Kyoko ; Mori, Hiroyuki ; Aki, Daisuke ; Ohishi, Masanobu ; Yoshida, Hiroki ; Kubo, Masato ; Yoshimura, Akihiko. / SOCS1/JAB is a negative regulator of LPS-induced macrophage activation. In: Immunity. 2002 ; Vol. 17, No. 5. pp. 583-591.
@article{8dc37301018549939b40e46cf1f53d3e,
title = "SOCS1/JAB is a negative regulator of LPS-induced macrophage activation",
abstract = "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-γ (IFNγ)-deficient background were more sensitive to LPS-induced lethal effects than were wild-type littermates. LPS-induced NO2- synthesis and TNFα 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-κB and p38 phosphorylation was upregulated in SOCS1-/- macrophages, and forced expression of SOCS1 suppressed LPS-induced NF-κB activation. Thus, SOCS1 directly suppresses TLR4 signaling and modulates innate immunity.",
author = "Ichiko Kinjyo and Toshikatsu Hanada and Kyoko Inagaki-Ohara and Hiroyuki Mori and Daisuke Aki and Masanobu Ohishi and Hiroki Yoshida and Masato Kubo and Akihiko Yoshimura",
year = "2002",
month = "11",
day = "1",
doi = "10.1016/S1074-7613(02)00446-6",
language = "English",
volume = "17",
pages = "583--591",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "5",

}

TY - JOUR

T1 - SOCS1/JAB is a negative regulator of LPS-induced macrophage activation

AU - Kinjyo, Ichiko

AU - Hanada, Toshikatsu

AU - Inagaki-Ohara, Kyoko

AU - Mori, Hiroyuki

AU - Aki, Daisuke

AU - Ohishi, Masanobu

AU - Yoshida, Hiroki

AU - Kubo, Masato

AU - Yoshimura, Akihiko

PY - 2002/11/1

Y1 - 2002/11/1

N2 - 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-γ (IFNγ)-deficient background were more sensitive to LPS-induced lethal effects than were wild-type littermates. LPS-induced NO2- synthesis and TNFα 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-κB and p38 phosphorylation was upregulated in SOCS1-/- macrophages, and forced expression of SOCS1 suppressed LPS-induced NF-κB activation. Thus, SOCS1 directly suppresses TLR4 signaling and modulates innate immunity.

AB - 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-γ (IFNγ)-deficient background were more sensitive to LPS-induced lethal effects than were wild-type littermates. LPS-induced NO2- synthesis and TNFα 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-κB and p38 phosphorylation was upregulated in SOCS1-/- macrophages, and forced expression of SOCS1 suppressed LPS-induced NF-κB activation. Thus, SOCS1 directly suppresses TLR4 signaling and modulates innate immunity.

UR - http://www.scopus.com/inward/record.url?scp=0036850946&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036850946&partnerID=8YFLogxK

U2 - 10.1016/S1074-7613(02)00446-6

DO - 10.1016/S1074-7613(02)00446-6

M3 - Article

C2 - 12433365

AN - SCOPUS:0036850946

VL - 17

SP - 583

EP - 591

JO - Immunity

JF - Immunity

SN - 1074-7613

IS - 5

ER -