Attenuation of pristimerin on TNF-α-induced endothelial inflammation

Authors：Liang, Jiang; Yuan, Shiwen; Wang, Xiaohua; Lei, Yan; Zhang, Xuemei; Huang, Mingcheng^*; Ouyang, Hui^*

Source：International Immunopharmacology, 2020, 82: 106326.

DOI：10.1016/j.intimp.2020.106326

• Pristimerin
• Endothelial cells
• Vascular inflammation

Objective: Pristimerin is known to have anti-cancer and anti-inflammatory activities; however, its therapeutic mechanism has not been described. In this study, to investigate the therapeutic mechanism of pristimerin, we examined the effect of pristimerin on TNF-alpha-induced endothelial inflammatory response both in vitro and in vivo. @@@ Methods: Leukocyte-endothelium Adhesion Assay was use to evaluate the endothelial cell-monocyte interaction. Western blotting was used to confirm protein expression. NF-kappa B p65 nuclear translocation in endothelial cells was detected using immunofluorescent microscopy. In vivo leukocyte infiltration was evaluated using acute lung inflammation model. @@@ Results: Pristimerin profoundly inhibited TNF-alpha-induced adhesion of monocytes to human endothelial cells and the leukocyte transmigration. Pristimerin dramatically inhibited the expression of TNF-alpha-induced endothelial adhesion molecules (intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)) and the pro-inflammatory cytokine (IL-6, IL-8 and monocyte chemoattractant protein-1 (MCP-1)). Pristimerin suppressed the penetration of the leukocyte in the acute lung injury mice model. Furthermore, pristimerin also suppressed the TNF-alpha-activated Nuclear factor kappa B (NF-kappa B) activation. @@@ Conclusions: Pristimerin has the anti-inflammatory properties in endothelial cells, at least in part, through the suppression of NF-kappa B activation, which may have a potential therapeutic effects for inflammatory vascular diseases.

• Institution
  1; 贵州大学; 中山大学