Chlamydia pneumoniae induces macrophage-derived foam cell formation by up-regulating acyl-coenzyme A: cholesterol acyltransferase 1.
In macrophages, the accumulation of cholesteryl esters synthesized by acyl-coenzyme A: cholesterol acyltransferase 1(ACAT1) plays a crucial role in foam cell formation, a hallmark of early atherosclerotic lesions. It is suggested that Chlamydia pneumoniae (C. pneumoniae) induces foam cell formation. However, the mechanism of foam cell formation induced by C. pneumoniae has not been fully elucidated. In this study, we found that C. pneumoniae increased the expression of acyl-coenzyme A: cholesterol acyltransferase 1(ACAT1) mRNA and protein in a dose-dependent manner in THP-1-derived macrophages exposed to low density lipoprotein (LDL). In addition, C. pneumoniae dose-dependently suppressed the expression of peroxisome proliferator-activated receptor gamma (PPAR gamma) mRNA and protein. Rosiglitazone, a specific PPAR gamma agonist, not only dose-dependently alleviated the down-regulation of PPAR gamma expression by C. pneumoniae infection, but also dose-dependently inhibited the C. pneumoniae-induced ACAT1 expression. Furthermore, higher doses of rosiglitazone (10 and 20 microM) suppressed the C. pneumoniae-induced foam cell formation from morphological (Oil red O staining) and biochemical (zymochemistry method) criteria. These results first demonstrate that C. pneumoniae induces macrophage-derived foam cell formation by up-regulating ACAT1 expression via PPAR gamma-dependent pathway, which may contribute to its pro-atherogenic properties.
He
Ping
P
Department of gerontology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jie-Fang Avenue, Wuhan 430022, Hubei Province, China.
Mei
Chunli
C
Cheng
Bei
B
Liu
Wei
W
Wang
Yanfu
Y
Wan
Jingjing
J
D002460:Cell Line; D016993:Chlamydophila pneumoniae / Q000276:immunology*; D005487:Foam Cells / Q000382:microbiology*; D006801:Humans; D008264:Macrophages / Q000382:microbiology*; D047495:PPAR gamma / Q000096:biosynthesis; D002785:Sterol O-Acyltransferase / Q000096:biosynthesis*
D047495:PPAR gamma; D002785:Sterol O-Acyltransferase; C493492:sterol O-acyltransferase 1