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

Mol Cell Biochem. 2016 Jan;411(1-2):1-10. doi: 10.1007/s11010-015-2563-3. Epub 2015 Sep 19.

Abstract

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.

Keywords: Chemokine; Cytokine; HCAEC; Vascular inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Neutralizing / immunology
  • Cell Adhesion Molecules / metabolism
  • Cells, Cultured
  • Coronary Vessels / cytology
  • Coronary Vessels / metabolism*
  • Cytokines / metabolism
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / metabolism*
  • Humans
  • Interleukin-27 / physiology*
  • MAP Kinase Signaling System
  • NF-kappa B / metabolism
  • Receptors, Tumor Necrosis Factor / immunology
  • Tumor Necrosis Factor-alpha / physiology*

Substances

  • Antibodies, Neutralizing
  • Cell Adhesion Molecules
  • Cytokines
  • Interleukin-27
  • NF-kappa B
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha