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| Content Provider | PubMed Central |
|---|---|
| Author | Pickens, Sarah R. Volin, Michael V. Mandelin, Arthur M. Kolls, Jay K. Pope, Richard M. Shiva, Shahrara |
| 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 microvascular endothelial cell (HMVEC) migration mediated through the PI3K/AKT1 pathway. Further, 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 (R) C. Neutralization of either IL-17 in RA synovial fluids or IL-17RC on HMVECs significantly reduces the induction of HMVEC migration by RA synovial fluid. Finally, RA synovial fluid immunoneutralized with IL-17 and VEGF does not reduce HMVEC migration beyond the effect detected with 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. |
| Related Links | http://dx.doi.org/10.4049/jimmunol.0903271 |
| Ending Page | 3241 |
| Page Count | 9 |
| Starting Page | 3233 |
| File Format | |
| ISSN | 00221767 |
| e-ISSN | 15506606 |
| Journal | Journal of immunology (Baltimore, Md. : 1950) |
| Issue Number | 6 |
| Volume Number | 184 |
| Language | English |
| Publisher Date | 2010-03-15 |
| Access Restriction | Open |
| Subject Keyword | Medicine(all) Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
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