组蛋白去乙酰化酶2参与生理浓度的糖皮质激素的抗炎效应  

HDAC7 is involved anti-inflammatory actin of physiological level of glucocorticoids

作　　者：尹园[1] 柳玉梅[1] 张维文[1] 张贵平[1] 张海宁[1] 

机构地区：[1]广州医科大学药理教研室,511436

出　　处：《实用医学杂志》2016年第22期3650-3653,共4页The Journal of Practical Medicine

基　　金：广东省自然科学基金资助项目(编号:2016A030313569);广州市教育局基金资助项目(编号:10A179)

摘　　要：目的:探讨组蛋白去乙酰化酶2(HDAC2)在生理浓度的糖皮质激素(GCs)抗炎效应中的作用。方法:脂多糖(LPS)(20 mg/L)孵育腹腔巨噬细胞诱导炎症反应。ELISA法测定细胞培养上清中炎症因子TNF-α和IL-1β水平;Western blot及Trans AM NF-κB p65试剂盒检测NF-κB核转位和NF-κB与DNA的结合活性。HDAC阻断剂TSA或HDAC2 si RNA用于观察抑制HDAC2活性后对生理浓度的氢化可的松抑制LPS诱导的炎症反应及NF-κB活化的影响。结果 :LPS浓度依赖性的刺激TNF-α、IL-1β的产生,生理浓度的氢化可的松对此有明显的抑制作用,而预先给予TSA或HDAC2 si RNA,明显减弱氢化可的松对LPS诱导的TNF-α和IL-1β释放的抑制作用。进一步研究显示,LPS明显诱导NF-κB的核转位及与DNA的结合。生理浓度的氢化可的松减弱LPS诱导的p65/DNA结合从而抑制NF-κB的活化过程。预先给予TSA或HDAC2si RNA则可以阻断氢化可的松对NF-κB活化的抑制作用。结论 :HDAC2参与了生理浓度的GCs的抗炎效应,其机制与HDAC2介导的NF-κB转录活性的抑制有关。Objective To investigate the role of HDAC2 in anti-inflammatory effect of physiological level of glucocorticoids. Methods Inflammation was induced by LPS （20 mg/L） in macrophages and the levels of TNF-a and IL-1β in supernatant were measured by ELISA. The nuclear translocation of NF-KB or the p65/DNA binding activity was detected by Western blot and TransAM NF-KB p65 kit, respectively. The effect of HDAC2 in inflammation and NF-KB activation were observed by using of TSA or HDAC2 siRNA. Results LPS concentration- dependently induced the productions of TNF-aand IL-1β in macrophages. The physiological level of hydrocortisone showed an inhibitory effect on the production of cytokines. Both of TSA and HDAC2 siRNA attenuated the inhibitory effect of physiological level of hydrocortisone on the productions of TNF-a and IL-1β induced by LPS. Furthermore, LPS induced the activation of NF-KB by increased nuclear translocation of p65 and increasing p65/DNA binding activity. Similarly, the physiological level of hydrocortisone down-regulated the activation of NF-KB by inhibiting the p65 bound to DNA, while, pretreatment of macrophages with TSA or HDAC2 siRNA abolished the inhibitory effect of physiological level of hydrocortisone on the activation of NF-KB. Conclusion HDAC2 participates the anti- inflammatory mechanisms of physiological levels of glucocorticoids by attenuating NF-KB activation.

关 键 词：生理浓度的糖皮质激素 HDAC2 炎症 NF—KB 

分 类 号：R96[医药卫生—药理学]