Chlamydia pneumoniae induces macrophage-derived foam cell formation via PPAR α and PPAR γ-dependent pathways

In the presence of low density lipoprotein (LDL), Chlamydia pneumoniae induces macrophage-derived foam cell formation, a typical pathological feature of early atherosclerosis. However, its mechanism has not been fully understood. Peroxisome proliferator-activated receptors (PPARs) are key regulators of macrophage lipid metabolism. This study therefore investigated the role that PPAR α and PPAR γ may play a role in C. pneumoniae-induced foam cell formation. Oil Red O staining and Lipid mass quantification showed that LDL-treated THP-1 macrophages infected with high doses of C. pneumoniae (5 × 105 and 1 × 106 IFU) resulted in the large accumulation of lipid droplets and markedly increased the ratio of intracellular cholesteryl ester (CE) to total cholesterol (TC) (>50%). The results of RT-PCR and Western blot indicated that C. pneumoniae infection dose-dependently suppressed the expression of PPAR α and PPAR γ at mRNA and protein levels in LDL-treated THP-1 macrophages. PPAR α (fenofibrate) and PPAR γ (rosiglitazone) agonists, inhibited the accumulation of intracellular CE by C. pneumoniae in a dose-dependent manner. Furthermore, C. pneumoniae-induced foam cell formation was significantly suppressed by higher doses of fenofibrate (20 and 50 μM) and rosiglitazone (10 and 20 μM). These results first reveal that C. pneumoniae induces foam cell formation via PPAR α and PPAR γ-dependent pathway, which may contribute to its pro-atherogenic properties.