PPAR γ-ACAT1途径在肺炎衣原体诱导巨噬细胞泡沫化中的作用

AIM: To investigate the expressions of perocisome proliferators-activated receptor γ (PPAR γ) and acy1-coenzyme A: cholesterol acyltransferase-1 (ACAT1), and to discuss the mechanisms and pathways of Chlamydia pneumoniae (C.pn)-induced macrophage foam cell formation. METHODS: THP-1-derived macrophages were incubated for 48h with or without C.pn (1×10^5 to 1×10^6 IFU) and/or rosiglitazone (1 to 20μmol/L), a specific PPAR γ agonist. Lipid droplets in cytoplasm were observed by oil red O staining. The contents of intracellular cholesterol ester were detected by enzyme-fluorescence. PPAR γ, ACAT1 mRNA and protein expressions were determined by RT-PCR and Western blotting, respectively. RESULTS: THP-1-derived macrophages infected with C.pn at concentration of 5×10^5 and 1×10^6 IFU resulted in the large accumulation of lipid droplets and the ratio of cholesteryl ester (CE) to total cholesterol (TC) was much higher than 50% when co-incubated with low density lipoprotein (LDL). C.pn up-regulated the expressions of ACAT1 mRNA and protein, and down-regulated the expressions of PPAR γ mRNA and protein in a concentration-dependent manner (P＜0.05). Rosiglitazone (10, 20μmol/L) markedly suppressed the accumulation of lipid droplets and CE by C.pn. Moreover, rosiglitazone inhibited the up-regulation of ACAT1 mRNA and protein expression by C.pn infection in a concentration-dependent manner (P＜0.05). CONCLUSION: C.pn induces macrophage foam cell formation by up-regulating ACAT1 expression via PPAR γ pathway, which may provide new evidences for the development and progression of atherosclerosis initiated by C.pn infection.