MAPK-PPAR alpha/gamma signal transduction pathways are involved in Chlamydia pneumoniae-induced macrophage-derived foam cell formation

作者：Cheng Bei; Wu Xiaohua; Sun Shan; Wu Qinqin; Mei Chunli; Xu Qiumei; Wu Jianping; He Ping^*

来源：Microbial Pathogenesis, 2014, 69-70: 1-8.

DOI：10.1016/j.micpath.2014.03.001

• Chlamydia pneumoniae
• Foam cells
• Peroxisome proliferator-activated receptors
• Mitogen-activated protein kinase
• Atherosclerosis

Chlamydia pneumoniae (C pneumoniae) is now widely accepted as an independent risk of atherosclerosis development. In this paper, our results showed that C. pneumoniae infection significantly increased the number of foam cells in LDL-treated THP-1 macrophages. C-Jun NH2 terminal kinase (JNK1/2) inhibitor SP600125 and extracellular signal-regulated kinase (ERK1/2) inhibitor PD98059 strongly inhibited C pneumoniae-induced accumulation of lipid droplet, whereas p38 inhibitor SB203580 had no obvious effect on lipid accumulation. Furthermore, we found that C pneumoniae not only stimulated the phosphorylation of Mitogen-activated protein kinase (MAPK) including JNK1/2, ERK1/2 and p38 but also down-regulated the expression of peroxisome proliferator-activated receptors (PPAR gamma and PPAR alpha) at mRNA and protein levels. However, the phosphorylation of JNK1/2, ERK1/2 and p38 MAPK by C pneumoniae was substantially reversed after PPAR gamma agonist (rosiglitazone) or PPAR alpha agonist (fenofibrate) treatment while PPAR gamma inhibitor (GW9662) and PPAR alpha antagonist (MK886) enhanced C pneumoniae-induced phosphorylation of JNK1/2, ERK1/2 and p38. In addition, we demonstrated that C pneumoniae-induced PPAR gamma and PPARa down-regulation were significantly suppressed by JNK1/2 inhibitor (SP600125) and ERK1/2 inhibitor (PD98059), but not p38 inhibitor (SB203580). These results first declare that MAPK-PPAR alpha/gamma reciprocal signal pathways are involved in C pneumoniae, which induces foam cell formation, thus facilitating atherogenesis.

• 出版日期2014-5
• 单位华中科技大学