Tanshinone I limits inflammasome activation of macrophage via docking into Syk to alleviate DSS-induced colitis in mice.
Mol Immunol
; 173: 88-98, 2024 Sep.
Article
em En
| MEDLINE
| ID: mdl-39088935
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-1ß 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 (4â¯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-1ß, 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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sulfato de Dextrana
/
Colite
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Abietanos
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Inflamassomos
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Quinase Syk
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Macrófagos
Limite:
Animals
Idioma:
En
Revista:
Mol Immunol
/
Mol. immunol
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Molecular immunology
Ano de publicação:
2024
Tipo de documento:
Article