肺炎衣原体下调THP-1源性巨噬细胞ABCA1、ABCG1表达的机制研究

AIM: 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 mole clues in cholesterol efflux 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 SF600125 for 1 h, and then infected with Cpn (1×l0^6 IFU) and 50 mg/L LDL; SF600125 group, SP600125 (20μmol/L) and 50mg/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-PPARγ signal transduction pathway.