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Sarm1 Controls the MYD88-Mediated Inflammatory Responses in Inflammatory Bowel Disease via the Regulation of TRAF3 Recruitment.
- Source :
-
Immunological investigations [Immunol Invest] 2024 Jul; Vol. 53 (5), pp. 800-812. Date of Electronic Publication: 2024 Apr 23. - Publication Year :
- 2024
-
Abstract
- Background: Sterile alpha and TIR motif-containing 1 (Sarm1) is known as a negative regulator of inflammatory responses. However, its role in inflammatory bowel disease (IBD) is still unclear.<br />Objective: This study aimed to explore the function of Sarm1 in IBD and its underlying mechanisms. Sarm1 and tumor necrosis factor (TNF) receptor associated factor 3 (TRAF3) knockout (KO) micewere established.<br />Methods: The colitis was induced using dextran sulfate sodium (DSS). Bone marrow-derived macrophages (BMDMs) were isolated and stimulated with lipopolysaccharides (LPS) or cytidine phosphate guanosine(CpG). Inflammatory cytokines were measured viaELISA. qPCR and Western blotting were used to determine the levels of the mRNA and protein expression, respectively.<br />Results: It was demonstrated that reduced expression of Sarm1 was correlated with the severity of IBD in ulcerative colitis patients, and also with the reduction of pro-inflammatory cytokines in the mouse model induced by DSS. It was further observed that Sarm1 KO enhanced the induction of pro-inflammatory cytokines in both animal and in vitro cell models. Sarm1 deficiency in macrophages increased the severity of colitis in the mouse model induced by DSS. Moreover, Sarm1 regulatedTRAF3 recruitment to myeloid differentiation primary response protein 88 (MyD88), which in turn controlled the MYD88-mediated inflammatory responses.<br />Conclusions: In summary, our data suggest that Sarm1 controls the MYD88-mediated inflammatory responses in IBD via its regulation of TRAF3 recruitment.
- Subjects :
- Animals
Mice
Humans
Male
Female
Mice, Inbred C57BL
Cytokines metabolism
Signal Transduction
Adult
Colitis immunology
Colitis metabolism
Colitis chemically induced
Colitis genetics
Colitis, Ulcerative immunology
Colitis, Ulcerative metabolism
Colitis, Ulcerative genetics
Colitis, Ulcerative chemically induced
Myeloid Differentiation Factor 88 metabolism
Myeloid Differentiation Factor 88 genetics
Mice, Knockout
Cytoskeletal Proteins metabolism
Cytoskeletal Proteins genetics
Armadillo Domain Proteins metabolism
Armadillo Domain Proteins genetics
Macrophages immunology
Macrophages metabolism
TNF Receptor-Associated Factor 3 metabolism
TNF Receptor-Associated Factor 3 genetics
Dextran Sulfate
Disease Models, Animal
Inflammatory Bowel Diseases immunology
Inflammatory Bowel Diseases metabolism
Inflammatory Bowel Diseases genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1532-4311
- Volume :
- 53
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Immunological investigations
- Publication Type :
- Academic Journal
- Accession number :
- 38651786
- Full Text :
- https://doi.org/10.1080/08820139.2024.2343889