Abstract 3540: Dual Role of Interleukin 17 in Vascular Dysfunction and Hypertension
Angiotensin II (Ang II) increases the number of T cells in the vessel wall, particularly in the adventitia and periadventitial fat. We have found that production of a unique cytokine, interleukin 17 (IL17), is increased in T cells from Ang II infused mice. The role of IL17, if any, in Ang II induced hypertension is unknown. We showed by RT-PCR that cultured human umbilical vein endothelial cells (HUVECs), human aortic smooth muscle cells (HASMs), and human visceral pre-adipocytes (HVPAs) express the IL17A receptor. By real time RT-PCR, we found that in HASMs and HVPAs but not HUVECs, IL17 treatment caused a marked reduction in the tumor necrosis factor alpha (TNFa) induced expression of ICAM-1 and VCAM-1. In HVPAs, IL17 treatment also caused a marked reduction in the TNFa induced RANTES expression. Using Western Blot analysis in HASMs, we confirmed that the TNFa induced increases in VCAM-1 and ICAM-1 protein levels are markedly reduced by co-treatment with IL17. To determine more broadly the panel of genes affected by IL17 in HUVECs and HASMs, we performed gene array analysis using the Illumina platform. Interestingly there were no genes significantly affected by IL17 treatment in HUVECs and only one gene, stanniocalcin-1, that was increased 1.75-fold in HASMs. Thus, in vascular cells, IL17 alone has little effect on gene expression but rather functions as a modulator of other cytokines such as TNFa. We then examined the effect of IL17 in vivo on Ang II induced hypertension using IL17 knockout (KO) mice. Interestingly, the hypertension induced by 4 weeks of Ang II was modestly reduced in IL17KO mice compared to wild type mice (159 mmHg ± 2.5 vs 170 mmHg ± 4; n = 5). Our results show that while IL17 may have a protective or anti-inflammatory role in aortic smooth muscle and pre-adipocytes by inhibiting TNFa induced increases in VCAM-1, ICAM-1, and RANTES gene expression, it is involved in promoting the late phase of Ang II induced hypertension in vivo. Thus, although classically considered a pro-inflammatory cytokine, IL17 appears to play a dual role in vascular dysfunction and hypertension.