JNK-PPARγ信号转导通路在肺炎衣原体诱导THP-1源性泡沫细胞形成中的作用

Role of JNK-PPARγ signal transduction pathway in THP-1-derived foam cell formation induced by Chlamydia pneumoniae

目的:观察c-Jun氨基末端激酶(JNK)-过氧化物酶体增殖因子活化受体γ(PPARγ)信号通路在肺炎衣原体(Cpn)诱导THP-1源性泡沫细胞形成的作用。方法:THP-1单核细胞诱导分化为巨噬细胞后随机分为5组:对照组、Cpn感染组、罗格列酮(PPARγ特异性激动剂)+Cpn组、GW9662(PPARγ特异性抑制剂)+Cpn组、SP600125(JNK特异性抑制剂)+Cpn组。免疫印迹法(Western blot)检测细胞磷酸化JNK(p-JNK)蛋白表达,并分别用逆转录聚合酶链反应(RT-PCR)法和Western blot法检测细胞PPAR-γmRNA和蛋白表达,油红O染色和酶荧光化学法检测泡沫细胞的形成。结果:Cpn可上调pJNK的表达,下调PPARγ表达;而SP600125可阻断Cpn对PPARγ表达的下调。罗格列酮及SP600125抑制Cpn诱导的THP-1源性泡沫细胞形成,而GW9662促进Cpn诱导的THP-1源性泡沫细胞形成。结论:肺炎衣原体通过JNK-PPARγ信号转导通路诱导THP-1源性泡沫细胞形成。

Objective：To investigate the role of the c-Jun NH2 terminal kinase （JNK）-peroxisome proliferator-activated receptor Gamma（PPARγ） signal transduction pathway in THP-1-derived foam cell formation induced by Chlamydia pneumonia（Cpn）.Methods：Cpn was propagated in Hep-2 cells.THP-1 monocytes were induced into macrophages by 160 nmol/L phorbol myristate acetate（PMA） for 48 h.THP-1-derived macrophages co-cultured with 50 μg/ml low density lipoprotein （LDL） were randomly allocated into five groups：control （uninfected） group,Cpn infection group,Cpn and rosiglitazone （a special PPARγagonist）group,Cpn and GW9662 （a special PPARγ inhibiter）group,Cpn and SP600125 （a special JNK inhibiter）group.The expressions of phospho-JNK and also PPARγ were determined by RT-PCR and Western blot,respectively.Lipid droplets in cytoplasm were observed by oil red O staining.The contents of intracellular cholesterol ester were detected by enzyme-fluorescence.Results：The expression of phospho-JNK in THP-1-derived macrophages were up-regulated by Cpn infection in a dose-dependent manner.Cpn down-regulated the expression of PPARγ,and induced THP-1-derived foam cell formation.However,the mentioned effects of Cpn infection could be restrained by the special JNK inhibiter SP600125.PPARγ agonist rosiglitazone suppressed THP-l-derived foam cell formation induced by Cpn,while PPARγ inhibiter GW9662 promoted that.Conclusion：Chlamydia pneumoniae may induce THP-l-derived foam cell formation via JNKPPARγ signal transduction pathway.