曲古菌素A对FcεRI介导的肥大细胞活化的影响

Effect of Trichostatin A on Activation of Mast Cells Mediated by FcεRI

曲古菌素A(TSA)是一种组蛋白去乙酰化酶抑制剂,在变态反应等免疫性疾病和抗肿瘤方面显示了潜在的治疗效应。主要观察了TSA对变态反应的效应细胞—肥大细胞活化的影响。TSA可诱导小鼠骨髓来源的肥大细胞(BMMC)凋亡,并抑制表面FcεRI的表达。TSA处理的BMMC经anti-IgE/IgE刺激之后,脱颗粒及分泌TNF-α、IL-6和IL-13生物活性介质的能力显著受到抑制。由此提示,TSA可能通过诱导BMMC凋亡和/或下调FcεRI表达,进而抑制FcεRI介导的BMMC活化,这为TSA进一步在肥大细胞相关的变态反应性疾病中的应用提供了实验数据。

Trichostatin A（TSA） a histone deacetylase inhibitor,has been shown to have potential therapeutic effects on immune diseases such as allergy and anti-tumor.In this report,the effects of TSA on the activation of mast cells were observed,the key element of allergic reaction.It was shown that TSA could induce the apoptosis of mouse bone marrow-derived mast cells（BMMC） and the down-regulation of surface FcεRI expression.TSA treated BMMC led to the reduced ability significantly of degranulation and secretion of cytokines including tumor necrosis factor（TNF）-α,interleukin（IL）-6 and IL-13 stimulated with anti-IgE/IgE.These results indicated that TSA treatment suppressed the activation of BMMC mediated by FcεRI supposedly via induction of apoptosis of BMMC and/or subsequently reduced surface expression of FcεRI,which would provide the new data for the application of TSA on mast cell-mediated allergic diseases.