Effects And Preliminary Mechanism Of SAA On SR-BI And Inflammatory Factor Expression In THP-1Macrophage

Objective: Scavenger receptor class B type I (SR-BI) is one of the most importantmembrane proteins， which mediated reverse cholesterol transport(RCT), hasprotective effect on atherosclerosis. A new study has been found that the inflammatoryresponse affect reverse cholesterol transporter, and then affect the incidence ofcholesterol efflux and atherosclerosis development. Serum amyloid A (SAA) caninduce the inflammatory response of human macrophage, and get a significantincrease in the expression of inflammation factors, such as IL-10, TNF-α, andIL-6,which induce by lipopolysaccharide. Additionally, SAA would reduce theanti-inflammatory effects of HDL, and promote the progress of atherosclerosis. Thisstudy was to investigate the inflammatory response and the regulation of SR-BIexpression in THP-1macrophage after treated by SAA, and discover the preliminarymechanisms.Methods: THP-1cells were cultured, treated with160nmol/L PMA for12hours andinduced the differentiation of macrophages. In serum-free medium, THP-1macrophages were treated with different concentrations of SAA (0,100,200,400,800ng/ml) for24hours, or were worked with400ng/ml SAA in different time (0,4,8,16,32hours), or were cultured with400ng/ml SAA and P38agonist (anisomycin) orinhibitors (SB203580) for24hours, respectively. We quantified the specific SR-BImRNA expression by real-time PCR. SR-BI and phosphosphorylated P38proteinexpression were measured by Western Blotting and cell immunohistochemical method.Then the protein expression of inflammatory factors (MCP-1, TNF-α, IL-1β) weremeasured by ELISA.Results: After treating the cells with SAA, the levels of inflammatory factors(MCP-1, TNF-α, IL-1β) were increased, and the mRNA and protein expression of SR-BI were down-regulated, and the protein expression of phosphorylated P38wereup-regulated, which compared with the blank control group. The effect was in the wayof concentration-dependent and time-dependent. After SAA and P38agonistprocessing cell, the expression of SR-BI was down-regulated, but the levels ofinflammatory factors and phosphorylated P38protein expression were increased,compared with the cells only treated by SAA. In contrast, the SR-BI expression wasup-regulated, inflammatory factor and phosphorylated P38protein expressiondecreased when the cells treated with SAA and P38inhibitors.Conclusions: SAA increased the levels of inflammatory factors (MCP-1, TNF-α, IL-1β), inhibited the expression of SR-BI, then promoted the inflammatory response inTHP-1macrophages; The effect of SAA may be associated with phosphorylation ofP38protein, the P38-MAPK signal pathway may be involved in the regulation ofSR-BI expression and the inflammatory reaction stimulated by SAA in THP-1macrophages.