Cited by 630Immune Response and InflammationCytokine Signaling Pathways and InteractionsNF-κB Signaling Pathways

SOCS1/JAB Is a Negative Regulator of LPS-Induced Macrophage Activation

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Kinjyo, Ichiko, Hanada, Toshikatsu, Inagaki-Ohara, Kyoko, Mori, Hiroyuki, Aki, Daisuke, Ohishi, Masanobu, Yoshida, Hiroki, Kubo, Masato +1 more·2002·Immunity

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-gamma (IFNgamma)-deficient background were more sensitive to LPS-induced lethal effects than were wild-type littermates. LPS-induced NO(2)(-) synthesis and TNFalpha 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-kappaB and p38 phosphorylation was upregulated in SOCS1(-/-) macrophages, and forced expression of SOCS1 suppressed LPS-induced NF-kappaB activation. Thus, SOCS1 directly suppresses TLR4 signaling and modulates innate immunity.

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Crossref · 10.1016/s1074-7613(02)00446-6

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Authors
Kinjyo, I., Hanada, T., Inagaki-Ohara, K., Mori, H., Aki, D., Ohishi, M., Yoshida, H., Kubo, M., & Yoshimura, A.
Affiliations
  • Kyushu University (JP)
  • Tokyo University of Science (JP)
Corresponding author
Yoshimura, Akihiko
Venue
Immunity
Publisher
Elsevier BV
Published
2002-11
Volume
17
Issue
5
Pages
583-591
ISSN
1074-7613 (ISSN-L)
OpenAlex
W2044153851
Cited by
630
References
56
Citations by year
2026: 4 · 2025: 9 · 2024: 21 · 2023: 15 · 2022: 9 · 2021: 16 · 2020: 13 · 2019: 17 · 2018: 19 · 2017: 21 · 2016: 19 · 2015: 19 · 2014: 22 · 2013: 26 · 2012: 42
FWCI
15.55
Type
journal article
Language
en
Open access
Locations
  • Immunity (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Japan Health Sciences Foundation
  • Waseda University
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Keywords
SOCS1, jab, lipopolysaccharide, macrophage activation, TLR4 signaling, innate immunity, negative regulation of signaling, endotoxin tolerance, endotoxic shock, NF-κB activation, TNF-α, nitric oxide, interferon-gamma, p38 MAPK, IκB phosphorylation
MeSH terms
Suppressor of Cytokine Signaling 1 Protein, Animals, Carrier Proteins, Cells, Cultured, Lipopolysaccharides, Macrophage Activation, Membrane Glycoproteins, Mice, Inbred C57BL, Phosphorylation, Receptors, Cell Surface, Repressor Proteins, Signal Transduction, NF-kappa B, Macrophages, Peritoneal, Drosophila Proteins, Suppressor of Cytokine Signaling Proteins, Toll-Like Receptors, Toll-Like Receptor 4, Mice

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