Interleukin-17 causes Rho-kinase-mediated endothelial dysfunction and hypertension. Academic Article uri icon


  • AIMS: Elevated levels of pro-inflammatory cytokine interleukin-17A (IL-17) are associated with hypertensive autoimmune diseases; however, the connection between IL-17 and hypertension is unknown. We hypothesized that IL-17 increases blood pressure by decreasing endothelial nitric oxide production. METHODS AND RESULTS: Acute treatment of endothelial cells with IL-17 caused a significant increase in phosphorylation of the inhibitory endothelial nitric oxide (NO) synthase residue threonine 495 (eNOS Thr495). Of the kinases known to phosphorylate eNOS Thr495, only inhibition of Rho-kinase prevented the IL-17-induced increase. IL-17 caused a threefold increase in the Rho-kinase activator RhoA, and this was prevented by an IL-17 neutralizing antibody. In isolated mouse aortas, IL-17 significantly increased eNOS Thr495 phosphorylation, induced RhoA expression, and decreased NO-dependent relaxation responses, all of which were prevented by either an IL-17 neutralizing antibody or inhibition of Rho-kinase. In mice, IL-17 treatment for 1 week significantly increased systolic blood pressure and this was associated with decreased aortic NO-dependent relaxation responses, increased eNOS Thr495 phosphorylation, and increased RhoA expression. Inhibition of Rho-kinase prevented the hypertension caused by IL-17. CONCLUSION: These data demonstrate that IL-17 activates RhoA/Rho-kinase leading to endothelial dysfunction and hypertension. Inhibitors of IL-17 or Rho-kinase may prove useful as anti-hypertensive drugs in IL-17-associated autoimmune diseases.

published proceedings

  • Cardiovasc Res

altmetric score

  • 10.25

author list (cited authors)

  • Nguyen, H., Chiasson, V. L., Chatterjee, P., Kopriva, S. E., Young, K. J., & Mitchell, B. M.

citation count

  • 175

complete list of authors

  • Nguyen, Hoanglan||Chiasson, Valorie L||Chatterjee, Piyali||Kopriva, Shelley E||Young, Kristina J||Mitchell, Brett M

publication date

  • March 2013