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Blood, 1 October 2009, Vol. 114, No. 14, pp. 3117-3126. Prepublished online as a Blood First Edition Paper on August 6, 2009; DOI 10.1182/blood-2009-02-203372. This Article Full Text Full Text (PDF) Supplemental Methods and Figures All Versions of this Article: blood-2009-02-203372v1 114/14/3117    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Google Scholar Articles by Choi, Y.-S. Articles by Kwon, Y.-G. PubMed PubMed Citation Articles by Choi, Y.-S. Articles by Kwon, Y.-G. Related Collections Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  VASCULAR BIOLOGY Interleukin-33 induces angiogenesis and vascular permeability through ST2/TRAF6-mediated endothelial nitric oxide production Yeon-Sook Choi1, Hyun-Jung Choi1, Jeong-Ki Min2, Bo-Jeong Pyun1, Yong-Sun Maeng1, Hongryeol Park1, Jihye Kim1, Young-Myeong Kim3, and Young-Guen Kwon1 1 Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul; 2 Therapeutic Antibody Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon; and 3 Vascular System Research Center, Kangwon National University, Chunchon, Republic of Korea 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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