1. Academic Validation
  2. Tanshinone I limits inflammasome activation of macrophage via docking into Syk to alleviate DSS-induced colitis in mice

Tanshinone I limits inflammasome activation of macrophage via docking into Syk to alleviate DSS-induced colitis in mice

  • Mol Immunol. 2024 Sep:173:88-98. doi: 10.1016/j.molimm.2024.07.007.
Chunmiao Hu 1 Xiaoli He 2 Huimin Zhang 3 Xiangyu Hu 1 Liting Liao 4 Minmin Cai 3 Zhijie Lin 3 Jie Xiang 5 Xiaoqin Jia 3 Guotao Lu 1 Weiming Xiao 1 Yisheng Feng 6 Weijuan Gong 7
Affiliations

Affiliations

  • 1 Department of Gastroenterology, Yangzhou Key Laboratory for Precision Treatment of Refractory Bowel Diseases, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou 225001, PR China.
  • 2 Kunshan Hospital of Traditional Chinese Medicine, Suzhou Key Laboratory of Integrated Traditional Chinese and Western Medicine of Digestive Diseases, Kunshan Affiliated Hospital of Yangzhou University, Kunshan, PR China.
  • 3 Department of Basic Medicine, School of Medicine, Yangzhou University, Yangzhou 225001, PR China.
  • 4 Department of Gastroenterology, Yangzhou Key Laboratory for Precision Treatment of Refractory Bowel Diseases, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou 225001, PR China; Department of Basic Medicine, School of Medicine, Yangzhou University, Yangzhou 225001, PR China.
  • 5 Department of Pharmacology, School of Medicine, Yangzhou University, Yangzhou 225001, PR China.
  • 6 Kunshan Hospital of Traditional Chinese Medicine, Suzhou Key Laboratory of Integrated Traditional Chinese and Western Medicine of Digestive Diseases, Kunshan Affiliated Hospital of Yangzhou University, Kunshan, PR China. Electronic address: fys2009@126.com.
  • 7 Department of Gastroenterology, Yangzhou Key Laboratory for Precision Treatment of Refractory Bowel Diseases, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou 225001, PR China; Department of Basic Medicine, School of Medicine, Yangzhou University, Yangzhou 225001, PR China; Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou 225001, PR China; Jiangsu Key Laboratory of Zoonosis, Yangzhou 225001, PR China. Electronic address: wjgong@yzu.edu.cn.
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.

Keywords

Colitis; Inflammasome; Macrophage; Syk; Tanshinone I.

Figures
Products