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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
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摘要 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.
出处 《中国免疫学杂志》 CAS CSCD 北大核心 2014年第2期145-149,共5页 Chinese Journal of Immunology
基金 国家自然青年科学基金项目(No.30900599)
关键词 肺炎衣原体 动脉粥样硬化 泡沫细胞 过氧化物酶体增殖物激活受体Γ C-JUN氨基末端激酶 Chlamydia pneumoniae Atherosclerosis Foam cell Peroxisome proliferator-activated receptor gamma c-Jun NH2-terminal kinase
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