ABSTRACT
To investigate the effect and mechanism of serum amyloid A (SAA) on the expression of scavenger receptor class B type I (SR-BI) and inflammatory response in THP-1 macrophages, the human THP-1 cells were treated with SAA and p38-MAPK agonist (anisomycin) or p38-MAPK inhibitor (SB203580). Then, the expressions of SR-BI, phosphorylated p38-MAPK and inflammatory factors (MCP-1, TNF-α, IL-1β) were examined by real-time quantitative PCR, Western blotting and ELISA, respectively. The results showed that, compared with control group, SAA increased the levels of inflammatory factors (MCP-1, TNF-α, IL-1β), down-regulated the expressions of SR-BI, and up-regulated the expression of phosphorylated p38-MAPK protein in a concentration- and time-dependent manner in THP-1 cells (P < 0.05). After treatment with SAA and p38-MAPK agonist (anisomycin) in THP-1 cells, the expression of SR-BI was down-regulated, and the levels of inflammatory factors and phosphorylated p38-MAPK protein expression were increased, compared with the group only treated by SAA (P < 0.05). In contrast, the SR-BI expression was up-regulated, whereas inflammatory factors and phosphorylated p38-MAPK protein expressions were decreased after the cells were treated with SAA and p38-MAPK inhibitor (SB203580) (P < 0.05). The results suggest that SAA-promoted inflammatory response in THP-1 macrophages may be through the phosphorylation of p38-MAPK and inhibition of SR-BI expression.
Subject(s)
Humans , Cell Line , Chemokine CCL2 , Inflammation , Interleukin-1beta , MAP Kinase Signaling System , Macrophages , Phosphorylation , Serum Amyloid A Protein , Tumor Necrosis Factor-alpha , p38 Mitogen-Activated Protein KinasesABSTRACT
<p><b>AIM</b>To study the expressions of scavenger receptor class B type I(SR-BI) and peroxisome proliferator-activated receptor gamma (PPARgamma) in atherosclerotic mini swine and provide a new mechanism for investigating the pathogenesis of atherosclerosis.</p><p><b>METHODS</b>Chinese mini swine were fed by a normal control diet or a high fat/high cholesterol diet for 12 months after common carotid artery injury induced by balloon denudation. Plasma total cholesterol(TC), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) were determined by commercially enzymatic methods every two months. The sections, which were taken from liver and abdominal aorta, were stained with hematoxylin eosin. The expressions of SR-BI and PPARgamma mRNA and protein in liver and aorta tissue were detected by reverse transcriptase-polymerase chain reaction (RT-PCR), Western blot and immunohistochemistry respectively.</p><p><b>RESULTS</b>At the end of 12 months, plasma TC, HDL-C and TG in HFHC mini swine were increased. There were fatty liver and atherosclerotic plaque in mini swine live and aorta respectively. The expression of SR-BI was upregulated in HFHC mini swine liver and aorta tissue.</p><p><b>CONCLUSION</b>HFHC may induce atherosclerosis and the expression of SR-BI and PPARgamma. Upregulating SR-BI expression may inhibit atherosclerosis. Increasing SR-BI expression in liver and aorta may accelerate SR-BI-mediated reverse cholesterol transport and develop a new anti-atherogenic strategy.</p>