MULTIFUNCTIONAL CYTOKINE EXPRESSION BY HUMAN CORONARY ENDOTHELIUM ANDREGULATION BY MONOKINES AND GLUCOCORTICOIDS

Human endothelium is capable of expressing a variety of molecules, inc luding cytokines and growth factors, critical to inflammation This asp ect of coronary endothelium has not been studied in detail. In this st udy, we report, for the first time, expression of multifunctional cyto kines by human coronary artery endothelial cells (HCAEC) and their reg ulation by inflammatory cytokines and glucocorticoids. We also compare d expression of cytokine transcripts in two additional cell lines deri ved from pulmonary artery (HPAEC) and umbilical vein (HUVEC) endotheli um. HCAEC expressed transcripts for interleukin 5 (IL-5), IL-6, IL-8, and monocyte chemotactic protein-1 (MCP-1) constitutively. Induction o f IL-1 alpha, IL-6, granulocyte-macrophage colony-stimulating factor ( GM-CSF), and MCP-1 was seen following treatment with TNF alpha. We fou nd no expression of IL-1RA, IL-2, IL-2, IL-13, TNF-alpha, or IFN-gamma in HCAEC. IL-1 beta and TNF-alpha synergistically induced IL-6 and GM -CSF and additively induced IL-8 and MCP-1 production, while IL-2, IL- 10, IFN-alpha, and IFN-gamma had little or no additional effects. Inte restingly, no IL-1 alpha or IL-5 protein product was found even after maximal stimulation of HCAEC. No significant differences were seen in the profile of cytokine genes expressed by HCAEC, HPAEC, or HUVEC. Glu cocorticoids inhibited IL-8 production from all three cell lines. This study demonstrates that human coronary endothelial cells are capable of expressing a wide variety of multifunctional cytokines which may be of relevance to vascular inflammation. (C) 1998 Academic Press.