Cynarin attenuates LPS-induced endothelial inflammation via upregulation of the negative regulator MKP-3

초록

Increasing clinical observations have revealed that non-resolving low-grade inflammation is linked to the pathogenesis of chronic inflammatory diseases. Intriguingly, low levels of the circulating bacterial endotoxin, lipopolysaccharide (LPS), appear to be one of the primary causes of persistent low-grade inflammation. Endothelial cells line the inner surface of blood vessels, therefore, even low levels of circulating LPS can directly activate these cells and elicit a series of specific cell responses, such as an increase in cell adhesion molecules and proinflammatory cytokine/chemokine expression. In endothelial cells, LPS exposure results in an inflammatory response via activation of NF-κB and MAPKs. Cynarin is a phytochemical found in artichokes and has several pharmacological properties that can be used for endothelial inflammation. In this study, we discovered that cynarin suppressed LPS-induced increases in vascular cell adhesion molecule-1 and inflammatory mediators, such as MCP-1, TNF-α, and IL-1β in EA.hy926 cells. Further studies revealed that cynarin inhibited the activation of the p38 and NF-κB pathways by inducing the negative regulator MKP-3 in LPS-stimulated EA.hy926 cells. In conclusion, we found that cynarin alleviated inflammation by upregulating MKP-3, a negative regulator of p38 and NF-κB, which might serve as an effective candidate for diseases related to endothelial inflammation.