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Articles by K Bachmaier
Total Records ( 1 ) for K Bachmaier
  J Xue , P. B Thippegowda , G Hu , K Bachmaier , J. W Christman , A. B Malik and C. Tiruppathi
 

Activation of NF-B is essential for protease-activated receptor-1 (PAR-1)-mediated ICAM-1 expression in endothelial cells. Here we show that PAR-1 activation induces binding of both p65/RelA and NFATc1 to the NF-B binding site localized in intron-1 of the ICAM-1 gene to initiate transcription in endothelial cells. We discovered the presence of two NF-B binding sites in intron-1 (+70, NF-B site 1; +611, NF-B site 2) of the human ICAM-1 gene. Chromatin immunoprecipitation results showed that thrombin induced binding of p65/RelA and of NFATc1 specifically to intronic NF-B site 1 of the ICAM-1 gene. Electrophoretic mobility shift and supershift assays confirmed the binding of p65/RelA and NFATc1 to the intronic NF-B site 1 in thrombin-stimulated cells. Thrombin increased the expression of ICAM-1-promoter-intron 1-reporter (–1,385 to +234) construct ~25-fold and mutation of intronic NF-B site 1 markedly reduced thrombin-induced reporter expression. Moreover, inhibition of calcineurin, knockdown of either NFATc1 or p65/RelA with siRNA significantly reduced thrombin-induced ICAM-1 expression and polymorphonuclear leukocyte adhesion to endothelial cells. In contrast, NFATc1 knockdown had no effect on TNF--induced ICAM-1 expression. Thus these results suggest that p65/RelA and NFATc1 bind to the intronic NF-B site 1 sequence to induce optimal transcription of the ICAM-1 gene in response to thrombin in endothelial cells.

 
 
 
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