IL-17 contributes to angiogenesis in rheumatoid arthritis

Sarah R. Pickens, Michael V. Volin, Arthur M. Mandelin, Jay K. Kolls, Richard M. Pope, Shiva Shahrara*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

133 Scopus citations

Abstract

Angiogenesis is an early and a critical event in the pathogenesis of rheumatoid arthritis (RA). Neovascularization is dependent on endothelial cell activation, migration and proliferation, and inhibition of angiogenesis may provide a novel therapeutic approach in RA. In this study, we document a novel role of IL-17 in mediating angiogenesis. Local expression of IL-17 in mouse ankles increases vascularity.We further demonstrate that IL-17 is angiogenic by showing its ability to promote blood vessel growth in Matrigel plugs in vivo. Additionally, IL-17, in concentrations present in the RA joint, induces human lung microvascular endothelial cell (HMVEC) migration mediated through the PI3K/AKT1 pathway. Furthermore, suppression of the PI3K pathway markedly reduces IL-17-induced tube formation. We also show that both IL-17-induced HMVEC chemotaxis and tube formation are mediated primarily through IL-17 receptor C. Neutralization of either IL-17 in RA synovial fluids or IL-17 receptor C on HMVECs significantly reduces the induction of HMVEC migration by RA synovial fluid. Finally, RA synovial fluid immunoneutralized with anti-IL-17 and antivascular endothelial growth factor does not reduce HMVEC migration beyond the effect detected by immunodepleting each factor alone. These observations identify a novel function for IL-17 as an angiogenic mediator in RA, supporting IL-17 as a therapeutic target in RA.

Original languageEnglish (US)
Pages (from-to)3233-3241
Number of pages9
JournalJournal of Immunology
Volume184
Issue number6
DOIs
StatePublished - Mar 15 2010

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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