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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 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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Metadata
- 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
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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