白介素13通过FOXA2调控气道上皮细胞粘液分泌  

IL-13 regulates mucus secretion via FOXA2 in vitro

作　　者：江德鹏[1] Victor P.Kolosov Juliy M.Perelman 周向东[1] 

机构地区：[1]重庆医科大学附属第二医院呼吸内科,重庆400010 [2]俄罗斯医学科学院西伯利亚分院远东国立生理学和呼吸病理学科学研究中心

出　　处：《中国免疫学杂志》2011年第2期99-102,共4页Chinese Journal of Immunology

基　　金：国家自然科学基金(30770951);国家自然科学基金中俄合作项目(81011120108);中国与俄罗斯政府间科技合作项目资助

摘　　要：目的:研究白介素13(Interleukin-13,IL-13)对气道上皮细胞粘液分泌的效应并探讨其作用机制。方法:HBE16细胞在无血清培养基中培养24小时后加入IL-13刺激24小时,ELISA检测粘蛋白(MUC)5AC的表达;Western检测磷酸化细胞外信号调节激酶1/2(Extracellular signal-regulated kinase 1/2,ERK1/2)和磷酸化c-Jun氨基端激酶1/2(c-Jun N-terminal kinase 1/2,JNK1/2的表达;使用SP600125阻滞JNK信号通路后检测MUC5AC蛋白表达;RT-PCR检测STAT4和STAT6的表达变化;EMSA检测通路下游核蛋白FOXA2的表达。结果:IL-13刺激24小时后MUC5AC和p-JNK1/2表达升高,而p-ERK1/2表达无显著变化;使用SP600125阻断JNK通路表达后,MUC5AC表达减弱;IL-13刺激后STAT4表达无显著变化,STAT6表达显著升高,FOXA2表达显著降低。结论:IL-13通过JNK-STAT6-FOXA2通路调控粘液分泌。Objective：To investigate the effect of interleukin-13（IL-13） on mucus secretion in vitro and the possible mechanism.Methods：HBE16 cells were serum-starved for 24 h and exposed to IL-13 for 24 h.The level of MUC5AC was detected using ELISA.The phosphorylation of extracellular signal-regulated kinase 1/2（ERK1/2） and c-Jun N-terminal kinase 1/2（JNK1/2） were also examined also.The cells were pretreated with SP600125 for 1 h and then the level of MUC5AC was measured.RT-PCR was performed to examine the mRNA level of STAT4 and STAT6.Electrophoretic mobility shift assays （EMSA） were performed to examine the DNA-binding activity of Forkhead box a2（FOXA2）.Results：IL-13 caused a significant increase of MUC5AC and p-JNK1/2,yet failed to affect the phosphorylation of ERK1/2.The expression of MUC5AC was attenuated after treatment with SP600125.A significant increase in STAT6 was observed in IL-13 group compared to that of the saline-treatment group,whereas the expression of STAT4 was not significantly affected.The DNA-binding activity of FOXA2 was down-regulated after exposed to IL-13.Conclusion：Our study suggestes that IL-13 down-regulates mucus secretion via JNK-STAT6FOXA2 pathway in vitro.

关 键 词：白介素13 C-JUN氨基端激酶 FOXA2蛋白 粘液 

分 类 号：Q291[生物学—细胞生物学]