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

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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, Yoshimura, Akihiko·2002·Immunity

DOI 10.1016/s1074-7613(02)00446-6

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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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Self-citation

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
ORCID: Kinjyo, Ichiko
Hanada, Toshikatsu
Mori, Hiroyuki
Kubo, Masato
Yoshimura, Akihiko
Venue: Immunity
Publisher: Elsevier BV
Published: 2002-11
Volume: 17
Issue: 5
Pages: 583-591
ISSN: 1074-7613 (ISSN-L)
DOI: 10.1016/s1074-7613(02)00446-6
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: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 3911 d)
Locations: Immunity (publishedVersion)
PubMed (publishedVersion)
Funders: Japan Health Sciences Foundation
Waseda University
Topics: Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Life Sciences › Immunology and Microbiology › Immunology › 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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SOCS1/JAB Is a Negative Regulator of LPS-Induced Macrophage Activation

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