PMID- 9633934 OWN - NLM STAT- MEDLINE DCOM- 19980708 LR - 20190831 IS - 1079-5642 (Print) IS - 1079-5642 (Linking) VI - 18 IP - 6 DP - 1998 Jun TI - IL-1beta-induced monocyte chemoattractant protein-1 gene expression in endothelial cells is blocked by proteasome inhibitors. PG - 934-40 AB - 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-1 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)-1beta 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-1beta induction of MCP-1 protein expression. norLeu and TPCK also blocked IL-1beta-induced MCP-1 promoter-driven reporter gene expression as well as nuclear factor (NF)-kappaB-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-kappaB translocation to the nucleus, norLeu had no effect on NF-kappaB nuclear translocation or IL-1beta-induced phosphorylation of p65. This study demonstrates that the proteasome pathway is involved in IL-1beta-induced MCP-1 gene expression in human endothelial cells. FAU - Parry, G C AU - Parry GC AD - Department of Immunology, The Scripps Research Institute, La Jolla, Calif, USA. FAU - Martin, T AU - Martin T FAU - Felts, K A AU - Felts KA FAU - Cobb, R R AU - Cobb RR LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Arterioscler Thromb Vasc Biol JT - Arteriosclerosis, thrombosis, and vascular biology JID - 9505803 RN - 0 (Chemokine CCL2) RN - 0 (Cysteine Proteinase Inhibitors) RN - 0 (Interleukin-1) RN - 0 (Leupeptins) RN - 0 (Multienzyme Complexes) RN - 0 (NF-kappa B) RN - 0 (Serine Proteinase Inhibitors) RN - 110044-82-1 (acetylleucyl-leucyl-norleucinal) RN - 402-71-1 (Tosylphenylalanyl Chloromethyl Ketone) RN - EC 3.4.22.- (Cysteine Endopeptidases) RN - EC 3.4.25.1 (Proteasome Endopeptidase Complex) SB - IM MH - Cells, Cultured MH - Chemokine CCL2/*genetics MH - Cysteine Endopeptidases/*metabolism MH - Cysteine Proteinase Inhibitors/pharmacology MH - Endothelium, Vascular/*metabolism MH - *Gene Expression Regulation MH - Humans MH - Interleukin-1/*physiology MH - Leupeptins/pharmacology MH - Multienzyme Complexes/*metabolism MH - NF-kappa B/metabolism MH - Proteasome Endopeptidase Complex MH - Serine Proteinase Inhibitors/*pharmacology MH - Tosylphenylalanyl Chloromethyl Ketone/pharmacology EDAT- 1998/06/20 00:00 MHDA- 1998/06/20 00:01 CRDT- 1998/06/20 00:00 PHST- 1998/06/20 00:00 [pubmed] PHST- 1998/06/20 00:01 [medline] PHST- 1998/06/20 00:00 [entrez] AID - 10.1161/01.atv.18.6.934 [doi] PST - ppublish SO - Arterioscler Thromb Vasc Biol. 1998 Jun;18(6):934-40. doi: 10.1161/01.atv.18.6.934.