Thrombin promotes proinflammatory phenotype in human vascular smooth muscle cell.
Expression of PAR, the thrombin receptor, is elevated in smooth muscle cell-rich areas in atherosclerotic plaques, where the cells change to proinflammatory or synthetic phenotype. In this study we investigated whether thrombin promotes a proinflammatory phenotype in vascular smooth muscle cell (VSMC), characterized by increased cytokine and chemokine synthesis. Thrombin not only elevated transcripts for IL-6, CXCL8, and CCL11 genes but also enhanced release of IL-6 and CXCL8 protein from human aortic smooth muscle cell (HAoSMC). Thrombin activated Akt, PKC and MAPK in HAoSMC, and thrombin-mediated expression of IL-6 and CXCL8 was significantly inhibited by LY294002, AKT IV, RO318220, and GF109203X as well as by diphenyleneiodium at the messenger RNA and the protein levels. SB202129 and U0126 also significantly attenuated thrombin-mediated release of IL-6 and CXCL8 proteins from HAoSMC. These results indicate that thrombin promotes proinflammatory phenotype in human VSMC and that PI3K, Akt, PKC, NADPH oxidase, and MAPK are involved in that process. We propose that activation VSMC in response to thrombin after endothelial injury and/or thrombus formation will enhance inflammation in vasculature.
Chung
Sung-Woon
SW
Department of Thoracic and Cardiovascular Surgery, School of Medicine, Pusan National University, Busan, Republic of Korea.
Park
Jae-Woo
JW
Lee
Sae-A
SA
Eo
Seong-Kug
SK
Kim
Koanhoi
K
D050197:Atherosclerosis / Q000201:enzymology* / Q000235:genetics; D002460:Cell Line; D006801:Humans; D007249:Inflammation / Q000201:enzymology* / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D019255:NADPH Oxidases / Q000378:metabolism; D010641:Phenotype; D011493:Protein Kinase C / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism* / Q000494:pharmacology; D015854:Up-Regulation
D015850:Interleukin-6; D016209:Interleukin-8; D019255:NADPH Oxidases; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D013917:Thrombin