肺炎衣原体下调THP-1源性巨噬细胞ABCA1、ABCG1表达的机制研究

Signal transduction mechanism of Chlamydia pneumoniae in down-regulating the expression of ABCA1 and ABCG1 from THP-1-derived macrophages

目的:观察c-Jun氨基末端激酶(JNK)对肺炎衣原体(Cpn)诱导的THP-1源性巨噬细胞ATP结合盒转运蛋白A1(ABCA1)、ATP结合盒转运蛋白G1(ABCG1)和过氧化物酶体增殖物激活受体γ(PPARγ)表达的调控作用,探讨Cpn下调THP-1源性巨噬细胞ABCA1/ABCG1表达的信号转导机制。方法:将THP-1单核细胞诱导分化为巨噬细胞后,观察Cpn感染对细胞内ABCA1/ABCG1及PPARγ mRNA和蛋白表达的影响。并用不同浓度的JNK特异性抑制剂SP600125对细胞进行预处理,观察SP600125对Cpn诱导的ABCA1/ABCG1、PPARγ mRNA和蛋白表达的影响。分别用RT-PCR和Western blotting检测各组ABCA1/ABCG1及PPARγ mRNA和蛋白表达。结果:Cpn下调THP-1源性巨噬细胞ABCA1/ABCG1及其上游调控基因PPARγ mRNA和蛋白表达。而SP600125能呈浓度依赖性地抑制Cpn感染所带来的上述影响。结论:Cpn可能通过JNK-PPARγ信号转导通路下调AB-CA1/ABCG1表达,减少巨噬细胞内胆固醇流出,促进动脉粥样硬化发生发展。

A1M： To investigate the signal transduction mechanism of Chlamydia pneumoniae （Cpn） in down - regulating the expression of ATP binding cassette A1 （ ABCA1 ） and ATP binding cassette G1 （ ABCG1 ）, the key molecules in cholesterol effiux and atherogenesis, from THP - 1 - derived macrophages. METHODS： Cpn was propagated in Hep - 2 cells. THP - 1 monocytes were induced into macrophages by 160 nmol/L phorbol myristate acetate （PMA） for 48 h, and were randomly allocated into 4 groups to incubate continually： control group, 50 mg/L low density lipoprotein （LDL） ; Cpn infection group, Cpn （1 ×10^6 IFU） and 50 mg/L LDL; Cpn and SP600125 （a special JNK inhibiter） group, THP - 1 macrophages were previously treated with different concentrations （1 -20μmol/L） of SP600125 for 1 h, and then infected with Cpn （1×106 IFU） and50 mg/L LDL; SP600125 group, SP600125 （20 μmol/L） and 50 mg/L LDL. The expressions of ABCA1/ABCG1 and peroxisome proliferator- activated receptor γ（PPARγ） from each group were detected then. The cholesterol efflux was detected by enzyme - fluorescence. The expressions of ABCA1/ABCG1 and PPARγ mRNA and protein were determined by RT - PCR and Western blotting, respectively. RESULTS： Cpn not only down - regulated the ABCA1/ABCG1 expression, but also down- regulated the expression of PPARγ, which regulated the ABCA1/ABCG1 genes transcriptions. However, the mentioned effects of Cpn infection were restrained by the special JNK inhibitor SP600125 in a dose- dependent manner. CONCLUSION： Chlamydia pneumoniae may down- regulate ABCA1/ABCG1 expression from THP - 1 - derived macrophages via JNK - PPARγsignal transduction pathway.