Back to Search
Start Over
Tanshinone I limits inflammasome activation of macrophage via docking into Syk to alleviate DSS-induced colitis in mice.
- Source :
-
Molecular Immunology . Sep2024, Vol. 173, p88-98. 11p. - Publication Year :
- 2024
-
Abstract
- Tanshinone I (Tan I) has been proven to exert an anti-inflammatory effect, but the complete mechanism remains unclear. In this study, Tan I was described to have no effect on Syk expression in resting or LPS-stimulated macrophages ex vivo , but dramatically suppressed Syk phosphorylation and CD80, CD86, and IL-1β expression of macrophages. The inflammatory activity of macrophages in ApoC3-transgenic (ApoC3TG) mice is upregulated by Syk activation. Tan I was determined to downregulate Syk phosphorylation and inflammatory activity of macrophages in ApoC3TG mice, both ex vivo and in vivo. Intraperitoneal injection of Tan I (4 mg/kg) effectively alleviated DSS-induced colitis in mice, accompanying with suppressing the activation of intestinal macrophages. Mechanistically, Tan I-treated macrophages exhibited a decrease in cytoplasmic ROS, NLRP3, GSDMD, and IL-1β, which suggested that the alternative pathway of inflammasome activation in macrophages was suppressed. The SPR assay demonstrated that Tan I bound to Syk protein with a dissociation constant (KD) of 2.473 × 10−6 M. When Syk expression was knocked down by its shRNA, the inhibitory effects of Tan I on macrophages were blocked. Collectively, Tanshinone I effectively alleviated DSS-induced colitis in mice by inhibiting Syk-stimulated inflammasome activation, hence suppressing the inflammatory activity of macrophages. • Tanshinone I inhibited p-Syk and limited the inflammatory activity of macrophages. • Tanshinone I effectively alleviated DSS-induced colitis in mice by limiting the activation of intestinal macrophages. • Tanshinone I-treated macrophages exhibited a decrease in alternative pathway of inflammasome activation. • Direct binding of Tanshinone Ⅰ to Syk was confirmed by the surface plasmon resonance assay. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01615890
- Volume :
- 173
- Database :
- Academic Search Index
- Journal :
- Molecular Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 179107464
- Full Text :
- https://doi.org/10.1016/j.molimm.2024.07.007