Exp Mol Med.  2009 Oct;41(10):757-764. 10.3858/emm.2009.41.10.082.

Interleukin-1beta promotes the expression of monocyte chemoattractant protein-1 in human aorta smooth muscle cells via multiple signaling pathways

Affiliations
  • 1Department of Immunology and Chronic Disease Research Center and Institute for Medical Science, School of Medicine, Keimyung University, Taegu 700-712, Korea. kwontk@dsmc.or.kr
  • 2Department of Internal Medicine and Biochemistry and Cell Biology, Kyungpook National University School of Medicine, Taegu 700-721, Korea.

Abstract

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.

Keyword

aorta; atherosclerosis; CCL2 protein, human; interleukin-1beta; myocytes, smooth muscle; NF-kappaB; protein kinase C; type C phospholipase

MeSH Terms

Active Transport, Cell Nucleus/drug effects
Aorta/pathology
Atherosclerosis/immunology/metabolism
Bridged Compounds/pharmacology
Cell Nucleus/*metabolism
Cells, Cultured
Chemokine CCL2/*biosynthesis
Estrenes/pharmacology
Genistein/pharmacology
Humans
Interleukin-1beta/metabolism
Myocytes, Smooth Muscle/drug effects/immunology/*metabolism/pathology
NF-kappa B/*metabolism
Phospholipases/antagonists & inhibitors
Protein-Tyrosine Kinases/antagonists & inhibitors
Pyrrolidinones/pharmacology
Recombinant Proteins/metabolism
Signal Transduction/*drug effects
Thiones/pharmacology
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