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Blood, 15 July 2007, Vol. 110, No. 2, pp. 519-528. Prepublished online as a Blood First Edition Paper on March 21, 2007; DOI 10.1182/blood-2006-08-040097. This Article Full Text Full Text (PDF) Supplemental Table and Figures All Versions of this Article: blood-2006-08-040097v1 blood-2006-08-040097v2 110/2/519    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 Citing Articles via Google Scholar Google Scholar Articles by Chiu, J.-J. Articles by Chien, S. Search for Related Content PubMed PubMed Citation Articles by Chiu, J.-J. Articles by Chien, S. Related Collections Cell Adhesion and Motility Gene Expression Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Mechanisms of induction of endothelial cell E-selectin expression by smooth muscle cells and its inhibition by shear stress Jeng-Jiann Chiu1,2, Li-Jing Chen1, Chih-I Lee1, Pei-Ling Lee1, Ding-Yu Lee1, Min-Chien Tsai1, Chia-Wen Lin1, Shunichi Usami3, and Shu Chien3,5 1 Division of Medical Engineering Research, National Health Research Institutes, Miaoli, Taiwan, Republic of China; 2 Institute of Biomedical Engineering, National Yang-Ming University, Taipei, Taiwan, Republic of China; 3 Department of Bioengineering 4 Department of Medicine 5 Whitaker Institute of Biomedical Engineering, University of California San Diego, La Jolla E-selectin is a major adhesion molecule expressed by endothelial cells (ECs), which are exposed to shear stress and neighboring smooth muscle cells (SMCs). We investigated the mechanisms underlying the modulation of EC E-selectin expression by SMCs and shear stress. SMC coculture induced rapid and sustained increases in expression of E-selectin and phosphorylation of interleukin-1 (IL-1) receptor-associated kinase glycoprotein-130, as well as the downstream mitogen-activated protein kinases (MAPKs) and Akt. By using specific inhibitors, dominant-negative mutants, and small interfering RNA, we demonstrated that activations of c-Jun-NH2-terminal kinase (JNK) and p38 of the MAPK pathways are critical for the coculture-induced E-selectin expression. Gel shifting and chromatin immunoprecipitation assays showed that SMC coculture increased the nuclear factor-B (NF-B)–promoter binding activity in ECs; inhibition of NF-B activation by p65-antisense, lactacystin, and N-acetyl-cysteine blocked the coculture-induced E-selectin promoter activity. Protein arrays and blocking assays using neutralizing antibodies demonstrated that IL-1ß and IL-6 produced by EC/SMC cocultures are major contributors to the coculture induction of EC signaling and E-selectin expression. Preshearing of ECs at 12 dynes/cm2 inhibited the coculture-induced EC signaling and E-selectin expression. Our findings have elucidated the molecular mechanisms underlying the SMC induction of EC E-selectin expression and the shear stress protection against this SMC induction. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. K. Hsiai Mechanosignal transduction coupling between endothelial and smooth muscle cells: role of hemodynamic forces Am J Physiol Cell Physiol, March 1, 2008; 294(3): C659 - C661. [Full Text] [PDF]

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