Interleukin-1beta promotes the expression of monocyte chemoattractant protein-1 in human aorta smooth muscle cells via multiple signaling pathways.
Monocyte chemoattractant protein-1 (MCP1) plays a key role in monocyte/macrophage infiltration to the sub-endothelial space of the blood vessel wall, which is a critical initial step in atherosclerosis. In this study, we examined the intracellular signaling pathway of IL-1beta-induced MCP1 expression using various chemical inhibitors. The pretreatment of a phosphatidylcholine (PC)-specific PLC (PC-PLC) inhibitor (D609), PKC inhibitors, or an NF-kapaB inhibitor completely suppressed the IL-1beta-induced MCP1 expression through blocking NF-gammaB translocation to the nucleus. Pretreatment with inhibitors of tyrosine kinase or PLD partially suppressed MCP1 expression and failed to block nuclear NF-kappaB translocation. These results suggest that IL-1beta induces MCP1 expression through activation of NF-kappaB via the PC-PLC/PKC signaling pathway.
Lim
Jun Hee
JH
Department of Immunology and Chronic Disease Research Center and Institute for Medical Science, School of Medicine, Keimyung University, Taegu 700-712, Korea.
Um
Hee Jung
HJ
Park
Jong-Wook
JW
Lee
In-Kyu
IK
Kwon
Taeg Kyu
TK
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D001011:Aorta / Q000473:pathology; D050197:Atherosclerosis / Q000276:immunology / Q000378:metabolism; D001952:Bridged-Ring Compounds / Q000494:pharmacology; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis*; D004963:Estrenes / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism*; D009636:Norbornanes; D010740:Phospholipases / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011760:Pyrrolidinones / Q000494:pharmacology; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013859:Thiocarbamates; D013871:Thiones / Q000494:pharmacology
D001952:Bridged-Ring Compounds; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D004963:Estrenes; D053583:Interleukin-1beta; D016328:NF-kappa B; D009636:Norbornanes; D011760:Pyrrolidinones; D011994:Recombinant Proteins; D013859:Thiocarbamates; D013871:Thiones; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C046498:tricyclodecane-9-yl-xanthogenate; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D010740:Phospholipases