TNF刺激肥大细胞IL-6分泌的信号转导通路

Signal transduction pathway for TNF-induced IL-6 release from mast cells

目的:检测TNF对肥大细胞IL-6、IL-10分泌和组胺释放的影响并探讨其可能的信号转导途径。方法:用不同浓度TNF激发肥大细胞系P815后收集细胞和上清,细胞用细胞激发信号ELISA(CASE)方法检测信号转导通路蛋白ERK、p38、和STAT3磷酸化水平,上清用ELISA检测组胺、IL-6和IL-10的水平。结果:ELISA结果显示TNF促进P815肥大细胞IL-6分泌(P<0.05),但对IL-10分泌和组胺释放无明显影响。ERK信号转导通路抑制剂PD98059和U0126抑制TNF引起的P815肥大细胞IL-6分泌(P<0.05),而p38信号转导通路抑制剂SB203580和STAT3信号转导通路抑制剂AG490不能抑制TNF引起的P815肥大细胞IL-6分泌。CASE结果显示ERK信号转导通路抑制剂PD98059,U0126抑制TNF引起的P815肥大细胞内ERK蛋白磷酸化(P<0.05)而p38信号转导通路抑制剂SB203580和STAT3信号转导通路抑制剂AG490不能抑制TNF引起的P815肥大细胞内p38和STAT3蛋白磷酸化。结论:TNF刺激小鼠肥大细胞P815分泌IL-6可能与ERK信号转导通路的激活有关的。

AIM： To investigate the effect of TNF on release of IL-6,IL-10 and histamine from mast cells and to explore its potential signal transduction pathway.METHODS： After stimulation of various concentrations of TNF,the P815 cells were analyzed by cellular activation of signal ELISA（CASE） to detect phosphorylation of ERK,p38 and STAT3,and the supernatants were collected and analyzed by ELISA to quantify release of IL-6,IL-10 and histamine from the cells.RESULTS： Compared with the untreated control,increased IL-6 release was detected in TNF-stimulated P815 cells（P〈0.05）.Pretreatment of PD98059 or U0126 inhibited TNF-induced IL-6 release and ERK phosphorylation in P815 cells（P〈0.05）,whereas pretreatment of SB203580 or AG490 hardly affect IL-6 release,with little effect on phosphorylation of p38 and STAT3 respectively.CONCLUSION： TNF induced IL-6 release from P815 cells may involve activation of ERK signalling pathway.