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Blood, 4 June 2009, Vol. 113, No. 23, pp. 6023-6033. Prepublished online as a Blood First Edition Paper on April 6, 2009; DOI 10.1182/blood-2008-10-183210. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-10-183210v1 113/23/6023    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 HighWire Citing Articles via CrossRef Google Scholar Articles by Cheranov, S. Y. Articles by Rao, G. N. PubMed PubMed Citation Articles by Cheranov, S. Y. Articles by Rao, G. N. Related Collections Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  VASCULAR BIOLOGY The 15(S)-hydroxyeicosatetraenoic acid-induced angiogenesis requires Janus kinase 2-signal transducer and activator of transcription-5B–dependent expression of interleukin-8 Sergey Y. Cheranov1, Dong Wang1, Venkatesh Kundumani-Sridharan1, Manjula Karpurapu1, Qiuhua Zhang1, Koteswara R. Chava1, and Gadiparthi N. Rao1 1 Department of Physiology, University of Tennessee Health Science Center, Memphis To understand the molecular basis underlying 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE)–induced angiogenesis, we have studied the role of the Janus kinase-signal transducer and activator of transcription (Jak-STAT) signaling. The 15(S)-HETE stimulated tyrosine phosphorylation of Jak2 in a time-dependent manner in human retinal microvascular endothelial cells (HRMVECs). Inhibition of Jak2 activation via adenovirus-mediated expression of its dominant-negative mutant attenuated 15(S)-HETE–induced HRMVEC migration and tube formation and Matrigel plug angiogenesis. Similarly, 15(S)-HETE activated tyrosine phosphorylation of STAT-5B in a time-dependent manner. Dominant-negative mutant-mediated interference of STAT-5B activation suppressed 15(S)-HETE–induced HRMVEC migration and tube formation and Matrigel plug angiogenesis. The 15(S)-HETE induced interleukin-8 (IL-8) expression in Jak2-STAT-5B–dependent manner in HRMVECs. In addition, neutralizing anti–IL-8 antibodies reduced 15(S)-HETE–induced HRMVEC migration and tube formation and Matrigel plug angiogenesis. Cloning and Transfac analysis of IL-8 promoter revealed the presence of 1 putative STAT-binding sequence at –476 nt, and electrophoretic mobility shift assay and chromatin immunoprecipitation analysis showed the binding of STAT-5B to this site in response to 15(S)-HETE. Mutational analysis showed that STAT binding site is essential for 15(S)-HETE–induced IL-8 promoter activity. Together, these observations suggest that 15(S)-HETE–induced angiogenesis requires Jak2-STAT-5B–dependent expression of IL-8. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. S. K. Potula, D. Wang, D. Van Quyen, N. K. Singh, V. Kundumani-Sridharan, M. Karpurapu, E. A. Park, W. C. Glasgow, and G. N. Rao Src-dependent STAT-3-mediated Expression of Monocyte Chemoattractant Protein-1 Is Required for 15(S)-Hydroxyeicosatetraenoic Acid-induced Vascular Smooth Muscle Cell Migration J. Biol. Chem., November 6, 2009; 284(45): 31142 - 31155. [Abstract] [Full Text] [PDF]

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