title: MAPK-PPARα/γ signal transduction pathways are involved in Chlamydia pneumoniae-induced macrophage-derived foam cell formation.
abstract: 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 (PPARγ and PPARα) at mRNA and protein levels. However, the phosphorylation of JNK1/2, ERK1/2 and p38 MAPK by C. pneumoniae was substantially reversed after PPARγ agonist (rosiglitazone) or PPARα agonist (fenofibrate) treatment while PPARγ inhibitor (GW9662) and PPARα antagonist (MK886) enhanced C. pneumoniae-induced phosphorylation of JNK1/2, ERK1/2 and p38. In addition, we demonstrated that C. pneumoniae-induced PPARγ and PPARα 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-PPARα/γ reciprocal signal pathways are involved in C. pneumoniae, which induces foam cell formation, thus facilitating atherogenesis.
authors.affiliation: Department of Gerontology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Bei
authors.initials: B
authors.lastname: Cheng
authors.affiliation: Department of Gerontology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Gerontology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Sun
authors.affiliation: Department of Gerontology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Qinqin
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Rheumatology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Chunli
authors.initials: C
authors.lastname: Mei
authors.affiliation: Department of Gerontology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Qiumei
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Gerontology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: doctorpeace74@gmail.com.
authors.forename: Ping
authors.initials: P
authors.lastname: He
mesh_terms: D002460:Cell Line; D016993:Chlamydophila pneumoniae / Q000276:immunology*; D005487:Foam Cells / Q000276:immunology* / Q000382:microbiology*; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D047493:PPAR alpha / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D047493:PPAR alpha; D047495:PPAR gamma; D020929:Mitogen-Activated Protein Kinase Kinases
keywords: Atherosclerosis; Chlamydia pneumoniae; Foam cells; Mitogen-activated protein kinase; Peroxisome proliferator-activated receptors