MIF抵抗糖皮质激素的抗炎效应及其机制  

The role of macrophage migration inhibitory factor in anti-inflammatory effects of glucocorticoids

作　　者：陈郑礼[1] 孙瑜[1] 王俊杰[1] 郦佳慧[1] 韩姝 夏照帆[1] 

机构地区：[1]第二军医大学附属长海医院烧伤科,上海200433

出　　处：《中国免疫学杂志》2013年第11期1146-1150,共5页Chinese Journal of Immunology

基　　金：国家自然科学基金(81000825)资助

摘　　要：目的:研究巨噬细胞移动抑制因子(Macrophage migration inhibitory factor,MIF)抵抗糖皮质激素的抗炎效应及其细胞内机制。方法:体外培养小鼠巨噬细胞系RAW264.7,用脂多糖(LPS)、MIF、地塞米松(Dex)分别或相继刺激RAW264.7细胞后,用ELISA方法检测上清液中前列腺素E2(PGE2)和白三烯B4(LTB4)含量的变化,Western blot方法检测RAW264.7细胞胞浆膜联蛋白Annexin 1的蛋白表达变化。结果:RAW264.7用MIF和LPS刺激以后,细胞释放脂质炎症介质PGE2和LTB4的量明显增加,Dex能明显减少PGE2和LTB4的产生,但加入外源性重组的MIF就可以逆转Dex的作用;LPS刺激能减少内源性Annexin 1的表达,加入Dex后能明显增加Annexin 1的表达,但是加入外源性重组的MIF以后,Dex增强Annexin 1表达的作用就被逆转。结论:MIF能抵抗糖皮质激素抑制脂质炎症介质PGE2和LTB4的释放,且部分是通过干扰Annexin1的表达实现的。Annexin 1可能是MIF抵抗糖皮质激素抗炎作用的关键靶点。Objective： To investigate the role of macrophage migration inhibitory factor（ MIF） on anti-inflammatory effects of glucocorticoids. Methods： RAW 264. 7 cells were stimulated with different concentrations of lipopolysaccharides（ LPS）,recombinant MIF and dexamethasone（ Dex）. Prostaglandin E2（ PGE2） and Leukotriene B4（ LTB4） production in cell supernatants were measured by ELISA and protein expression of Annexin 1 was evaluated by Western blot. Results： Treatment of recombinant MIF or LPS led to secretion of PGE2and LTB4in RAW 264. 7 macrophages in a concentration-dependent manner. Dex could decrease the secretion of PGE2and LTB4from RAW 264. 7 macrophages,while the inhibition of Dex on PGE2and LTB4production was counter-regulated when MIF was added. Stimulation of RAW 264. 7 macrophages with LPS resulted in a down-regulation of Annexin 1,while Dex or Dex plus LPS led to a significant up-regulation of Annexin 1 expression. The effect of Dex on Annexin 1 was counter-regulated by the administration of recombinant MIF. Conclusion： MIF counter-regulates the effects of glucocorticoids on PGE2and LTB4production possibly through interfering with expression of Annexin 1 in macrophages. Annexin 1 may be a key target for MIF negatively regulation of antiinflammatory effects of glucocorticoids.

关 键 词：巨噬细胞移动抑制因子 糖皮质激素 ANNEXIN 1 

分 类 号：R392.5[医药卫生—免疫学]