SOCS1/JAB Is a Negative Regulator of LPS-Induced Macrophage Activation
Open accessAbstract
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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Increased levels of miR-155 promotes pro-inflammatory cytokine secretion by targeting SOCS1 message for degradation and downregulating anti-inflammatory cytokines that act via JAK/STAT pathway and NF-kB signaling.
“Increased levels of miR-155 promotes pro-inflammatory cytokine secretion by targeting the Suppressor of Cytokine Signaling 1 (SOCS1) message for degradation and downregulating anti-inflammatory cytokines that act via the JAK/STAT pathway [27, 47] and NF-kB signaling [48].”
From Microglia specific deletion of miR-155 in Alzheimer’s disease mouse models reduces amyloid-β pathology but causes hyperexcitability and seizures (2023) · cites this paper as [47]
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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
- bronze
- doi.org
- Licence
- 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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