1.Interleukin-1beta promotes the expression of monocyte chemoattractant protein-1 in human aorta smooth muscle cells via multiple signaling pathways.
Jun Hee LIM ; Hee Jung UM ; Jong Wook PARK ; In Kyu LEE ; Taeg Kyu KWON
Experimental & Molecular Medicine 2009;41(10):757-764
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-kappaB inhibitor completely suppressed the IL-1beta-induced MCP1 expression through blocking NF-kappaB 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.
Active Transport, Cell Nucleus/drug effects
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Aorta/pathology
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Atherosclerosis/immunology/metabolism
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Bridged Compounds/pharmacology
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Cell Nucleus/*metabolism
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Cells, Cultured
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Chemokine CCL2/*biosynthesis
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Estrenes/pharmacology
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Genistein/pharmacology
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Humans
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Interleukin-1beta/metabolism
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Myocytes, Smooth Muscle/drug effects/immunology/*metabolism/pathology
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NF-kappa B/*metabolism
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Phospholipases/antagonists & inhibitors
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Protein-Tyrosine Kinases/antagonists & inhibitors
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Pyrrolidinones/pharmacology
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Recombinant Proteins/metabolism
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Signal Transduction/*drug effects
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Thiones/pharmacology