Interleukin-27 enhances TNF-α-mediated activation of human coronary artery endothelial cells

Immune cells and inflammatory mediators play important roles in the development of atherosclerotic vascular inflammation. IL-27 is a member of the IL-6/IL-12 family that can promote Th1 responses and augment the release of inflammatory mediators from human mast cells and monocytes. However, the direct effect of IL-27 on human coronary artery endothelial cells was unclear. In this study, the effects of IL-27 and TNF-α on the cell surface expression of adhesion molecules, inflammatory cytokines, and chemokines were investigated. Results showed that IL-27 alone could significantly promote the release of chemokine CXCL10. However, IL-27 could further significantly enhance the TNF-α-mediated upregulation of adhesion molecules ICAM-1 and VCAM-1, inflammatory cytokine IL-6, as well as chemokines CCL5 and CXCL10 from human coronary artery endothelial cells. The release of IL-6, CCL5, and CXCL10 were significantly suppressed by specific signaling molecule inhibitors, implying that the induction of these mediators from the human coronary artery endothelial cells could be differentially regulated by the c-Jun N-terminal kinase, p38 mitogen-activated protein kinase, and nuclear factor-κB pathways. These results provided new insights into the effect of IL-27 on the TNF-α mediated activation of human coronary artery endothelial cells in atherosclerotic vascular inflammation.