ArticleThe Journal of biological chemistry2016
Induction of Siglec-1 by Endotoxin Tolerance Suppresses the Innate Immune Response by Promoting TGF-β1 Production.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Mammalian Neuraminidases in Immune-Mediated Diseases: Mucins and Beyond.Frontiers in immunology · 2022Pooled it
- Siglec-1-targeted nanobodies restrict HIV-1 transmission and infection of dendritic cells.Journal of virology · 2026Article
- Loss of erythrocyte sialic acid in sepsis disrupts inhibitory Siglec interactions, driving neutrophil hyperactivation and NET outspread.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- In silico and in vitro investigations of novel Siglec-1 inhibitors in a microglial cell model.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- M2-Like Macrophages Exhibit Sialic Acid-Enhanced Efferocytosis via the Siglec CD22.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Tracing the evolutionary pathway of SARS-CoV-2 through RNA sequencing analysis.Scientific reports · 2025Article
- Comprehensive analysis of sialylation-related genes and construct the prognostic model in sepsis.Scientific reports · 2024Article
- Discovery, classification, evolution and diversity of Siglecs.Molecular aspects of medicine · 2023Review
- Sialidase Inhibitors with Different Mechanisms.Journal of medicinal chemistry · 2022Review
- The role of the Siglec-G ITIM domain during bacterial infection.Cellular and molecular biology (Noisy-le-Grand, France) · 2022Article
- Sialic Acid-Siglec Axis as Molecular Checkpoints Targeting of Immune System: Smart Players in Pathology and Conventional Therapy.International journal of molecular sciences · 2020Review
- Porcine sialoadhesin suppresses type I interferon production to support porcine reproductive and respiratory syndrome virus infection.Veterinary research · 2020Article
- Ganglioside Synthesis by Plasma Membrane-Associated Sialyltransferase in Macrophages.International journal of molecular sciences · 2020Article
- Article
- Persistent reduction in sialylation of cerebral glycoproteins following postnatal inflammatory exposure.Journal of neuroinflammation · 2018Article
- Microglial-specific transcriptome changes following chronic alcohol consumption.Neuropharmacology · 2018Article
- Sialic Acids in the Immune Response during Sepsis.Frontiers in immunology · 2017Review
- Development of Sialic Acid-coated Nanoparticles for Targeting Cancer and Efficient Evasion of the Immune System.Theranostics · 2017Article
- Siglec-E Negatively Regulates the Activation of TLR4 by Controlling Its Endocytosis.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Sepsis is one of the leading causes of death worldwide. Although the prevailing theory for the sepsis syndrome is a condition of uncontrolled inflammation in response to infection, sepsis is increasingly being recognized as an immunosuppressive state known as endotoxin tolerance. We found sialylation of cell surface was significantly increased on LPS-induced tolerant cells; knockdown of Neu1 in macrophage cell line RAW 264.7 cells resulted in enhanced LPS-induced tolerance, whereas overexpression of Neu1 or treatment with sialidase abrogated LPS-induced tolerance, as defined by measuring TNF-α levels in the culture supernatants. We also found that the expression of Siglec-1 (a member of sialic acid-binding Ig (I)-like lectin family members, the predominant sialic acid-binding proteins on cell surface) was specifically up-regulated in endotoxin tolerant cells and the induction of Siglec-1 suppresses the innate immune response by promoting TGF-β1 production. The enhanced TGF-β1 production by Siglec-1 was significantly attenuated by spleen tyrosine kinase (Syk) inhibitor. Knockdown of siglec-1 in RAW 264.7 cells resulted in inhibiting the production of TGF-β1 by ubiquitin-dependent degradation of Syk. Mechanistically, Siglec-1 associates with adaptor protein DNAX-activation protein of 12 kDa (DAP12) and transduces a signal to Syk to control the production of TGF-β1 in endotoxin tolerance. Thus, Siglec-1 plays an important role in the development of endotoxin tolerance and targeted manipulation of this process could lead to a new therapeutic opportunity for patients with sepsis.
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Registered trials
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