Histone Deacetylase Inhibitors Suppress TF-κB-dependent Agonist-driven Tissue Factor Expression in Endothelial Cells and Monocytes

Jianguo Wang, Shawn A. Mahmud, Peter B. Bitterman, Yuqing Huo, Arne Slungaard
2007 Journal of Biological Chemistry  
Histone deacetylase inhibitors (HDACi), such as trichostatin A (TSA), can regulate gene expression by promoting acetylation of histones and transcription factors. Human tissue factor (TF) expression is partly governed by a unique, NF-B-related "TF-B" promoter binding site. We find that TSA and four other HDACi (apicidin, MS-275, sodium butyrate, and valproic acid) all inhibit by ϳ90% TF activity and protein level induction in human umbilical vein endothelial cells stimulated by the physiologic
more » ... gonists tumor necrosis factor (TNF)-␣, interleukin-1␤, lipopolysaccharide, and HOSCN without affecting expression of the NF-B-regulated adhesion molecules ICAM-1 and E-selectin. TSA and butyrate also blunt TF induction ϳ50% in vitro in peripheral blood mononuclear cells and in vivo in thioglycolateelicited murine peritoneal macrophages. In human umbilical vein endothelial cells, TSA attenuates by ϳ70% TNF-␣ stimulation of TF mRNA transcription without affecting that of ICAM-1. By electrophoretic mobility shift assay analyses, TNF-␣ and lipopolysaccharide induce strong p65/p50 and p65/
doi:10.1074/jbc.m703586200 pmid:17675290 fatcat:7xfhylkcpfh67bbx2bfkrhk4vq