IL-1β-induced monocyte chemoattractant protein-1 gene expression in endothelial cells is blocked by proteasome inhibitors

被引:43
作者
Parry, GCN
Martin, T
Felts, KA
Cobb, RR
机构
[1] Tanabe Res Labs, Dept Biol, San Diego, CA 92121 USA
[2] Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA
关键词
monocyte chemoattractant protein-1; endothelial cells; proteasome inhibitors;
D O I
10.1161/01.ATV.18.6.934
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Human monocyte chemoattractant protein-1 (MCP-1) is expressed by a variety of cell types in response to various stimuli. MCP-1 expressed by the endothelium plays an important role in cell migration and activation. MCP-I is a major chemoattractant for monocytes, T lymphocytes, and basophils. In the present study, we present evidence that the proteasome complex is involved in mediating the interleukin (IL)-1 beta induction of MCP-1 in endothelial cells. We present evidence that a proteasome inhibitor, N-acetyl-leucinyl-leucinyl-norleucinal (norLeu), and the protease inhibitor tosyl-Phe-chloromethylketone (TPCK) block IL-1 beta induction of MCP-1 protein expression. norLeu and TPCK also blocked IL-1 beta-induced MCP-1 promoter-driven reporter gene expression as well as nuclear factor (NF)-kappa B-mediated reporter gene expression. The effects of norLeu were due to its inhibition of the proteasome rather than calpain, because other calpain inhibitors had no effect on MCP-1 expression. In contrast to TPCK, which blocked NF-KB translocation to the nucleus, norLeu had no effect on NF-kappa B nuclear translocation or IL-1 beta-induced phosphorylation of p65. This study demonstrates that the proteasome pathway is involved in IL-1 beta-induced MCP-1 gene expression in human endothelial cells.
引用
收藏
页码:934 / 940
页数:7
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