| First Author | Choi YS | Year | 2009 |
| Journal | Blood | Volume | 114 |
| Issue | 14 | Pages | 3117-26 |
| PubMed ID | 19661270 | Mgi Jnum | J:153371 |
| Mgi Id | MGI:4365315 | Doi | 10.1182/blood-2009-02-203372 |
| Citation | Choi YS, et al. (2009) Interleukin-33 induces angiogenesis and vascular permeability through ST2/TRAF6-mediated endothelial nitric oxide production. Blood 114(14):3117-26 |
| abstractText | Interleukin-33 (IL-33), a member of the IL-1 cytokine family, is emerging as a new regulator of immune responses and inflammatory vascular diseases. Although IL-33 and its cognate receptor ST2 appear to be expressed in vascular cells, the precise role of IL-33 in the vasculature has not been determined. In this study, we report a novel role of IL-33 as a potent endothelial activator, promoting both angiogenesis and vascular permeability. IL-33 increased proliferation, migration, and morphologic differentiation of human endothelial cells, consistently with increased angiogenesis in vivo. IL-33 also increased endothelial permeability with reduced vascular endothelial-cadherin-facilitated cell-cell junctions in vitro and induced vascular leakage in mouse skin. These effects of IL-33 were blocked by knockdown of ST2. Ligation of IL-33 with ST2 rapidly increased endothelial nitric oxide (NO) production through TRAF6-mediated activation of phosphoinoside-3-kinase, Akt, and endothelial NO synthase. Moreover, pharmacologic or genetic blockage of endothelial NO generation resulted in the inhibition of angiogenesis and vascular hyperpermeability induced by IL-33. These data demonstrate that IL-33 promotes angiogenesis and vascular leakage by stimulating endothelial NO production via the ST2/TRAF6-Akt-eNOS signaling pathway. These findings open new perspectives for the role of IL-33 in the pathogenesis of angiogenesis-dependent and inflammatory vascular diseases. |
