Interleukin‐17A plays an important role in endothelial cell activation and atherogenesis in ApoE−/− mice

Abstract

Interleukin‐17 (IL‐17) cytokines are a family of pro‐inflammatory cytokines. IL‐17A has been implicated in numerous autoimmune and inflammatory diseases including atherosclerosis. However, the role of IL‐17A in early atherogenesis remained to be determined. The objective of our study is to determine the role of IL‐17A in early atherogenesis. Previously, using a bioinformatics approach, we found that IL‐17 receptors A and C, and adaptor protein, ACT1, are expressed in human vascular tissue, suggesting that IL‐17A has a role in chronic vascular inflammation. The data for the expression of these receptors and ACT1 were not available in mouse vascular tissue; however, using immunostaining, we found that IL‐17RA is expressed in mouse aorta. Moreover, plasma levels of IL‐17A are found to be increased in atherogenic ApoE−/− mice compared with wild type mice. IL‐17A treatment was found to induce pro‐inflammatory cytokines production in mouse aortic cells. Furthermore, to elucidate the role of IL‐17A in atherogenesis in ApoE−/− mice, we cross‐bred IL‐17A−/− mice with ApoE−/− mice to generate our double knock‐out mouse model, ApoE−/−IL‐17A−/− mice. Our data suggest that IL‐17A have an important role in early atherogenesis and with our novel mouse model we will be able to elucidate the function as well as the mechanism of IL‐17A in the endothelial cell activation and development of atherosclerosis in ApoE−/− mice.