糖基化终产物对人单核细胞源树突状细胞丝裂原激活蛋白激酶表达的影响  

Study on Advanced Glycosylation End Products Affecting the Expression of Mitogen-activated Protein Kinase in Human Monocyte Derived Dendritic Cells

作　　者：贾庆哲[1] 葛均波[1] 梁春[2] 黄东[1] 姚康[1] 陈灏珠[1] 曹克将[3] 

机构地区：[1]上海市心血管病研究所复旦大学附属中山医院心内科,上海200032 [2]第二军医大学长征医院心内科,上海200003 [3]南京医科大学第一附属医院江苏省人民医院心内科,江苏南京210029

出　　处：《中国临床医学》2008年第1期1-4,共4页Chinese Journal of Clinical Medicine

基　　金：国家重点基础研究发展规划资助项目(G2000056903);上海市科委资助项目(02JC14026)

摘　　要：目的:探讨糖基化终产物(AGEs))对人单核细胞源树突状细胞(MDCs)丝裂原激活蛋白激酶表达的影响,探索AGEs在动脉粥样硬化免疫炎症反应中的作用。方法:免疫磁珠法分离人外周血CD14+单核细胞,经含重组人粒-巨噬细胞集落刺激因子(rhGM-CSF)(100ng·mL-1)和重组人白细胞介素-4(rhIL-4)(50ng·mL-1)的RPMI1640培养,使其分化为MDCs,用200μg·mL-1AGE-BSA干预DCs0,10,20,30,40min,采用Western-Blot,检测丝裂原激活蛋白激酶(MAPK),即磷酸化Erk、磷酸化Jnk、磷酸化P38MAPK的表达。结果:AGE-BSA刺激磷酸化Erk、磷酸化Jnk、磷酸化p38MAPK的表达,20min达到高峰,30min后开始下降,并且Jnk抑制剂SP600125明显抑制了AGE-BSA促进的糖基化终产物受体(RAGE)的表达。结论:AGEs能够激活MAPK信号途径,其中Jnk信号途径与RAGE的表达有关,这可能是AGEs通过树突状细胞促进动脉粥样硬化炎症免疫反应发生的重要机制之一。Objective：To explore the effect of advanced glycosylation end products （AGEs） on the expression of mitogen-acti-vated protein kinase in human monocyte-derived dendritic cells （MDCs）. Methods： Monocytes were purified （over 98%） using Anti-CD14^＋ microbeads, after eight days culture in RPMI1640 medium containing recombinated human granulocyte-macro- phage colony stimulating factor （rhGM-CSF） （100 ng·mLˉ^1） and recombinated human interleukin-4 （rhIL-4） （50 ng·mLˉ^1 ）, immature DCs were derived. At the eighth day, they were exposed to 200μg· mLˉ^1AGE-BSA for 0, 10, 20, 30 and 40 minutes,mitogen-activated protein kinase （MAPK）, i.e. Phospho-Erk, phospho- Jnk and Phospho-p38MAPK were measured by Western-blot. Results： Increases in the phosphoylation levels of Erk, Jnk and P38 were visible at 10 minutes, peaked at 20 minutes and declined thereafter. Jnk inhibitor SP600125 inhibited the expression of receptor for advanced glycosylation end products in DCs by AGEs inducing evidently. Conclusion： AGEs can activate the MAPK signal pathway. The expressions of RAGE have a relation with Jnk signal pathway. It may be one of the mechanisms of AGEs inducing atherosclerosis via DCs.

关 键 词：树突状细胞 动脉粥样硬化 糖基化终产物 丝裂原激活蛋白激酶 

分 类 号：R392.11[医药卫生—免疫学]