Study on up-regulation of the expression of cholesterol acyltransferase 1 induced by chlamydia pneumoniae via c-Jun N-terminal kinase signal transduction pathway / 中华老年医学杂志

ABSTRACT

Objective To investigate the role of c-Jun N-terminal kinase (JNK) signal transduction pathway on the up-regulation of the expression of acyl-coenzyme A cholesterol acyltransferasel (ACAT1) induced by Chlamydia pneumoniae (C. pn), and to discuss the mechanism of macrophages-derived foam cell formation induced by C. pn. Methods C. pn was propagated in Hep-2 cells. THP-1 monocytes were induced into macrophages by 160 nmol/L phorbol myristate acetate(PMA) for 48 h, and were randomly allocated into four groups to be incubated continually control group, C. pn infection group, C. pn and SP600125 (a special JNK inhibitor)group and SP600125 group. Lipid droplets in cytoplasm were observed by oil red O staining. The contents of intracellular cholesterol ester were detected by enzyme fluorescence analysis. The expressions of ACAT1 mRNA and protein were determined by reverse transcriptase polymerase chain reaction(RT-PCR) and Western blot, respectively. Results Compared with the control group, the expressions of ACAT1 mRNA and protein were up-regulated in C. pn infection group [(4.16±0.26) vs. (2.17±0.18), (1.20±0.10)vs. (0.61±0.03), both P<0.05], and C. pn-induced foam cell formation was observed. The expressions of ACAT1 mRNA and protein and the foam cell formation were inhibited by SP600125 in a concentration-dependent manner (r = - 0.92, P<0.05; r= - 0. 96, P<0.05, respectively). Conclusions The up-regulation of ACAT1 expression is induced by C. pn via JNK signal transduction pathway, which is involved in the mechanism of C. pn-induced macrophage-derived foam cell formation.