血清淀粉样蛋白A经p38-MAPK/SR-BI途径促进巨噬细胞炎症反应  

Serum amyloid A promotes the inflammatory response via p38-MAPK/SR-BI pathway in THP-1 macrophages

作　　者：朱明燕[1,2] 王燕[3] 王毓[4] 彭凤玲[1] 欧含笑 郑翔[1] 石金凤[1] 曾高峰[2] 莫中成[1] 

机构地区：[1]南华大学医学院组织学与胚胎学教研室,衡阳421001 [2]南华大学附属第二医院心血管内科,衡阳421001 [3]南华大学附属第二医院麻醉科,衡阳421001 [4]南华大学附属第二医院检验科,衡阳421001

出　　处：《生理学报》2016年第3期293-300,共8页Acta Physiologica Sinica

基　　金：supported by grants from the National Natural Science Foundation of China(No.81100211);the Natural Science Foundation of Hunan Province;China(No.14JJ2084;14JJ5016);the Science and Technology Project of Hengyang City;Hunan Province;China(No.2013KJ04);the Construct Program of the Key Discipline in Hunan Province;China(Basic Medicine Sciences in University of South China);Zhengxiang Scholar Program of the University of South China

摘　　要：为探讨血清淀粉样蛋白A(serum amyloid A,SAA)对巨噬细胞B类I型清道夫受体(scavenger receptor class B type I,SR-BI)的表达以及炎症反应的影响及分子机制,采用SAA、p38丝裂原活化蛋白激酶(p38 mitogen-activated protein kinase,p38-MAPK)激动剂anisomycin或抑制剂SB203580处理THP-1巨噬细胞,以实时定量PCR、Western blot和ELISA分别检测细胞中SR-BI、炎症因子及磷酸化p38-MAPK的表达。结果显示,与对照组相比,SAA处理THP-1细胞后,SR-BI的表达下调,而炎症因子与磷酸化p38蛋白的表达则上调,且这种效应呈浓度和时间依赖性(P<0.05)。与SAA单独处理组比较,SAA与p38-MAPK激动剂anisomycin共孵育细胞后,细胞SR-BI表达下调,炎症因子及磷酸化p38蛋白表达增加(P<0.05);而SAA与p38-MAPK抑制剂SB203580共同处理细胞后,细胞SR-BI表达增加,炎症因子及磷酸化p38蛋白表达减少(P<0.05)。结果提示,SAA可促进THP-1巨噬细胞炎症反应,其机制与p38-MAPK的磷酸化及SR-BI表达的下调有关。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.

关 键 词：B类I型清道夫受体 血清淀粉样蛋白A P38丝裂原活化蛋白激酶 动脉粥样硬化 

分 类 号：R392[医药卫生—免疫学]