[Chlamydia pneumoniae induces THP-1-derived foam cell formation by up-regulating the expression of acyl-coenzyme A: cholesterol acyltransferase 1].
OBJECTIVE
To investigate the expression changes of acyl-coenzyme A: cholesterol acyltransferase 1 (ACAT1) on Chlamydia pneumoniae (C.pn) induced foam cell formation.


METHODS
Human monocytic cell line (THP-1) was induced into macrophages by 160 nmol/L phorbol myristate acetate (PMA) for 48 h, and were randomly allocated into four groups: negative control group (50 microg/ml LDL for 48 h); positive control group (50 microg/ml ox-LDL for 48 h); C.pn infection group (50 microg/ml LDL plus 1 x 10(5), 4 x 10(5), 5 x 10(5) and 1 x 10(6) IFU C.pn for 48 h or 1 x 10(6) IFU C.pn for 0, 24, 48 and 72 h); ACAT inhibitor 58-035 plus C.pn infection group (1, 5, 10 microg/ml ACAT inhibitor 58-035 pretreatment for 1 h, 50 microg/ml LDL and 1 x 10(6) IFU C.pn for 48 h). The mRNA and protein expressions of ACAT1 were determined by RT-PCR and Western blot, respectively. Lipid droplets in cytoplasm were observed by oil red O staining. The contents of intracellular cholesteryl esters were detected by enzyme-fluorescence.


RESULTS
The mRNA and protein expressions of ACAT1 were significantly up-regulated in positive control cells compared those in negative control cells and further upregulated by C.pn infection in a time-dependent and concentration-dependent manner (all P < 0.05). There were significantly increases in the accumulation of lipid droplets and the ratio of cholesteryl ester to total cholesterol in positive control cells as compared with negative control cells and these were further aggravated by C.pn (at the concentrations of 5 x 10(5) and 1 x 10(6) IFU for 48 h) and C.pn infection induced increases in the accumulation of lipid droplets and the ratio of cholesteryl ester to total cholesterol could be significantly attenuated by ACAT inhibitor 58-035 (all P < 0.05).


CONCLUSIONS
Chlamydia pneumoniae induces THP-1-derived foam cell formation by up-regulating the expression of ACAT1.
Department of Gerontology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Ping
P
He
Chun-li
CL
Mei
Bei
B
Cheng
Wei
W
Liu
Yan-fu
YF
Wang
Jing-jing
JJ
Wan
D045744:Cell Line, Tumor; D016993:Chlamydophila pneumoniae; D005487:Foam Cells / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D009000:Monocytes / Q000166:cytology; D002785:Sterol O-Acyltransferase / Q000378:metabolism*; D015854:Up-Regulation
D002785:Sterol O-Acyltransferase