桂林医学院组胚教研室,南华大学附二医院,南华大学附二医院,衡阳市中心医院,南华大学附二医院,南华大学附二医院,南华大学附二医院,南华大学附二医院,南华大学附二医院
湖南省自然科学基金课题 (14JJ5016)
University of South China,The Second Affiliated Hospital of University of South China,The Second Affiliated Hospital of University of South China,The Central Hospital of HengYang,The Second Affiliated Hospital of University of South China,The Second Affiliated Hospital of University of South China,The Second Affiliated Hospital of University of South China,The Second Affiliated Hospital of University of South China,The Second Affiliated Hospital of University of South China
This work was supported by a grant from Hunan Provincial Natural Science Foundation (14JJ5016)
为探讨肝X受体α (LXRα)-三磷酸腺苷结合盒转运体A1 (ABCA1)途径在肺炎衣原体 (C. pneumoniae)促巨噬细胞脂质蓄积中的作用和机制,以THP-1巨噬细胞源性泡沫细胞为模型,采用高效液相色谱分析细胞内总胆固醇、游离胆固醇和胆固醇酯含量,液体闪烁计数器检测细胞内胆固醇流出,RT-PCR检测ABCA1和LXRα mRNA的表达,蛋白质印迹检测ABCA1和LXRα的蛋白质表达;使用LXRα的特异性激动剂T0901317对细胞进行预处理,再观察上述指标的变化.结果显示,C. pneumoniae可促进THP-1巨噬细胞源性泡沫细胞内总胆固醇、游离胆固醇和胆固醇酯含量增加,抑制胆固醇外流,降低细胞ABCA1和LXRα的表达;使用ABCA1激动剂8-溴-环磷酸腺苷预处理细胞或LXR激动剂T0901317预处理细胞后,可明显减弱C. pneumoniae对THP-1细胞ABCA1的表达抑制,促进细胞胆固醇流出,降低细胞内胆固醇的含量.结果提示,C. pneumoniae促进巨噬细胞脂质蓄积及胆固醇流出障碍,其机制可能与LXRα-ABCA1途径有关.
In order to investigate the roles and mechanisms of liver X receptor alpha (LXRα)-ATP binding cassette transporter A1 (ABCA1) pathway in Chlamydia pneumoniae (C. pneumoniae) infection induced macrophage lipid accumulation. THP-1 macrophage derived foam cells were used as the cell model. Cellular cholesterol was determined by high performance liquid chromatography analysis. Cholesterol efflux was determined by liquid scintillator. ABCA1 and LXRα mRNA expression was detected by RT-PCR and protein expression was detected by Western blot. Furthermore, we pretreated the cells with LXRα specific agonist T0901317, and then observed the changes of indexes mentioned above. The result showed that C. pneumoniae infection could increase the content of total cholesterol, free cholesterol and cholesterol ester, inhibit the efflux of cholesterol from cells, and reduce the expression of ABCA1 and LXRα. The suppression of C. pneumoniae infection on ABCA1 expression was significantly attenuated after the use of ABCA1 agonist 8-Br-cAMP or LXR agonist T0901317, correspondingly, cholesterol efflux was promoted and the content of intracellular cholesterol was elevated. These results suggested that the mechanism of C. pneumoniae infection promoting lipid accumulation in macrophages and suppresses cholesterol efflux may be related to LXRα-ABCA1 pathway.
赵国军,喻思扬,刘洋,唐业华,曾志英,石小桥,陈莹,曾高峰,王燕.研究: 肺炎衣原体抑制LXRα-ABCA1途径促进巨噬细胞脂质蓄积[J].生物化学与生物物理进展,2015,42(9):858-865
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