The Effect Of C-reactive Protein On The Expression Of Monocyte Chemoattractant Protein Induced Protein3in The Macrophages

Background:C-reactive protein (CRP) is closely related with coronary heart disease. The plasma CRP levels in patients with acute coronary syndrome increased obviously. Substantial evidence shows that CRP participates in the formation of atherosclerosis. CRP can induce inflammatory response in monocytes/macrophages which plays an important role in the occurrence and development of atherosclerosis. Monocyte chemoattractant protein-1(MCP-1) is an important chemokine in recruitment of monocytes/macrophages in atherosclerosis. A new protein was discovered in the human peripheral blood mononuclear cells which were treated by MCP-1, and then it was named monocyte chemoattractant protein-induced protein1(MCP-induced protein1, MCPIP1) in2006. Another three members in the same family were found gradually and designated as MCPIP2, MCPIP3and MCPIP4. It was demonstrated that MCPIP1inhibited inflammatory response in vascular endothelial cells and macrophages. Recently, the inhibitory role of MCPIP3in vascular endothelial cell inflammation was also found. However, the potential role of MCPIP3in inflammatory response in macrophages induced by CRP is unclear. Objectives:(1) To detect MCPIP3gene expression in peripheral blood mononuclear cells (PBMCs) in patients with acute coronary syndrome.(2) To explore the potential effect of CRP on MCPIP3gene expression in monocytes-derived macrophages.Methods:(1) PBMCs were isolated by density-gradient centrifugation from bloods of patients with acute coronary syndrome or without coronary heart diseases. The mRNA level of MCPIP3was measured by real-time quantitative PCR.(2) THP-1monocytes were differentiated to macrophages by adding160nM phorbol12-myristate13-acetate (PMA) for48h. Then the cells were divided into four groups to be incubated with different doses of CRP (0,5,12.5,25μg/mL). Total RNA was isolated from four groups of macrophages following treatments for24h. The mRNA levels of MCPIP3, interleukin-8(IL-8), interleukin-1β(IL-1β), interleukin-10(IL-10) were measured by real-time quantitative PCR.Results:(1) MCPIP3mRNA level in peripheral blood mononuclear cells of patients with acute coronary syndrome was significantly lower than that of patients without coronary heart diseases (P<0.05)(2)CRP significantly up-regulated the mRNA levels of pro-inflammatory cytokines, IL-8and IL-1β, and anti-inflammatory cytokines, IL-10(P<0.05, respectively), while significantly down-regulated MCPIP3mRNA level (P<0.05)Conclusions:(1) MCPIP3gene expression was down-regulated in peripheral blood mononuclear cells of patients with acute coronary syndrome.(2) MCPIP3gene expression reduced obviously during CRP-induced inflammation response in monocytes-derived macrophages.