肺炎衣原体通过TLR2-核因子-κB和miR-33途径对THP-1巨噬细胞源性泡沫细胞中ABCA1的表达起负调控作用。
Chlamydia pneumoniae negatively regulates ABCA1 expression via TLR2-Nuclear factor-kappa B and miR-33 pathways in THP-1 macrophage-derived foam cells.
作者信息
Zhao Guo-Jun, Mo Zhong-Cheng, Tang Shi-Lin, Ouyang Xin-Ping, He Ping-Ping, Lv Yun-Cheng, Yao Feng, Tan Yu-Lin, Xie Wei, Shi Jin-Feng, Wang Yan, Zhang Min, Liu Dan, Tang Deng-Pei, Zheng Xi-Long, Tian Guo-Ping, Tang Chao-Ke
机构信息
Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Life Science Research Center, University of South China, Hengyang 421001, China; Department of Histology and Embryology, Guilin Medical University, Guilin, Guangxi 541004, China.
Department of Histology and Embryology, University of South China, Hengyang, Hunan 421001, China.
出版信息
Atherosclerosis. 2014 Aug;235(2):519-25. doi: 10.1016/j.atherosclerosis.2014.05.943. Epub 2014 Jun 9.
OBJECTIVES
ATP-binding cassette transporter A1 (ABCA1) is critical in exporting cholesterol from macrophages and plays a protective role in the development of atherosclerosis. This study was to determine the effects and potential mechanisms of Chlamydia pneumoniae (C. pneumoniae) on ABCA1 expression and cellular cholesterol efflux in THP-1 macrophage-derived foam cells.
METHODS AND RESULTS
C. pneumoniae significantly decreased the expression of ABCA1 and reduced cholesterol efflux. Furthermore, we found that C. pneumoniae suppressed ABCA1 expression via up-regulation of miR-33s. The inhibition of C. pneumoniae-induced NF-κB activation decreased miR-33s expression and enhanced ABCA1 expression. In addition, C. pneumoniae increased Toll-like receptor 2 (TLR2) expressions, inhibition of which by siRNA could also block NF-κB activation and miR-33s expression, and promot the expression of ABCA1.
CONCLUSION
Taken together, these results reveal that C. pneumoniae may negatively regulate ABCA1 expression via TLR2-NF-κB and miR-33 pathways in THP-1 macrophage-derived foam cells, which may provide new insights for understanding the effects of C. pneumoniae on the pathogenesis of atherosclerosis.
目的
ATP结合盒转运体A1（ABCA1）在巨噬细胞胆固醇输出过程中起关键作用，对动脉粥样硬化的发展具有保护作用。本研究旨在确定肺炎衣原体（C. pneumoniae）对THP-1巨噬细胞源性泡沫细胞中ABCA1表达及细胞胆固醇流出的影响和潜在机制。
方法与结果
肺炎衣原体显著降低ABCA1的表达并减少胆固醇流出。此外，我们发现肺炎衣原体通过上调miR-33s抑制ABCA1表达。抑制肺炎衣原体诱导的NF-κB激活可降低miR-33s表达并增强ABCA1表达。另外，肺炎衣原体增加Toll样受体2（TLR2）的表达，用小干扰RNA抑制TLR2也可阻断NF-κB激活和miR-33s表达，并促进ABCA1的表达。
结论
综上所述，这些结果表明肺炎衣原体可能通过TLR2-NF-κB和miR-33途径对THP-1巨噬细胞源性泡沫细胞中ABCA1的表达产生负调控作用，这可能为理解肺炎衣原体对动脉粥样硬化发病机制的影响提供新的见解。
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