Mechanisms of induction of endothelial cell E-selectin expression by smooth muscle cells and its inhibition by shear stress

Jeng Jiann Chiu, Li Jing Chen, Chih I. Lee, Pei Ling Lee, Ding Yu Lee, Min Chien Tsai, Chia Wen Lin, Shunichi Usami, Shu Chien

研究成果: 雜誌貢獻文章同行評審

54 引文 斯高帕斯(Scopus)

摘要

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 and 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-κB (NF-κB)-promoter binding activity in ECs; inhibition of NF-κB 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-1β 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.

原文英語
頁(從 - 到)519-528
頁數10
期刊Blood
110
發行號2
DOIs
出版狀態已發佈 - 七月 15 2007
對外發佈

ASJC Scopus subject areas

  • 生物化學
  • 免疫學
  • 血液學
  • 細胞生物學

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