TY - JOUR T1 - Combination of IL-17 and TNFα induces a pro-inflammatory, pro-coagulant and pro-thrombotic phenotype in human endothelial cells JF - Annals of the Rheumatic Diseases JO - Ann Rheum Dis SP - 768 LP - 776 DO - 10.1136/annrheumdis-2011-200468 VL - 71 IS - 5 AU - Arnaud Hot AU - Vanina Lenief AU - Pierre Miossec Y1 - 2012/05/01 UR - http://ard.bmj.com/content/71/5/768.abstract N2 - Objective Cardiovascular events remain the leading cause of death in rheumatoid arthritis (RA). To study the role of cytokines in these observations, the effects of tumour necrosis factor α (TNFα) and interleukin (IL)-17, a classical and a new key player in RA, were assessed in endothelial cell (EC) dysfunction. Methods Primary human EC were treated with IL-17 alone or combined with TNFα. mRNA expression was quantified by qRT PCR and Affymetrix microarrays. The role of IL-17 was studied using functional assays of platelet aggregation, EC migration and invasion. Results IL-17 alone induced 248 pro-inflammatory genes and 9803, when combined with TNFα. IL-17 plus TNFα induced synergistically chemokine genes such as CCL5, IL-8 and cytokine genes such as IL-6. In contrast, IL-17 decreased genes involved in the regulation of inflammation such as IL-33. IL-17 induced EC migration and invasion in synergy with TNFα. Such invasion was inhibited with an antiCXCR4 antibody, indicating the contribution of the stromal cell-derived factor-1/C-X-C chemokine receptor type 4 axis. Supernatants of IL-17-treated EC induced strong platelet aggregation. IL-17 inhibited endothelial CD39/ATPDase expression, an inhibitor of platelet activation. Finally, IL-17 enhanced genes critical for coagulation such as tissue factor and decreased thrombomodulin, leading to a pro-thrombotic state. Conclusion These results indicate that IL-17 specifically when combined with TNFα has major pro-coagulant and pro-thrombotic effects on vessels. ER -