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
发布时间：2018-12-07 08:04
【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。
[Abstract]:Aim: to investigate the role of histone deacetylase 2 (HDAC2) in anti-inflammatory effects of glucocorticoid (GCs). Methods: lipopolysaccharide (LPS) () was incubated with peritoneal macrophages for 20 mg/L to induce inflammatory response. The levels of TNF- 伪 and IL-1 尾 in the supernatant of cell culture were measured by ELISA method. Western blot and Trans AM NF- 魏 B p65 kit were used to detect the nuclear translocation of NF- 魏 B and the binding activity of NF- 魏 B to DNA. TSA or HDAC2 si RNA, a HDAC blocker, was used to observe the inhibition of LPS induced inflammation by hydrocortisone on the physiological concentration of HDAC2. The reaction and the activation of NF- 魏 B. Results: LPS stimulated the production of TNF- 伪 and IL-1 尾 in a concentration-dependent manner. Hydrocortisone inhibited the production of TNF- 伪 and IL-1 尾 in a dose-dependent manner, but was pretreated with TSA or HDAC2 si RNA,. The inhibitory effect of hydrocortisone on TNF- 伪 and IL-1 尾 release induced by LPS was significantly reduced. Further studies showed that LPS significantly induced the nuclear translocation of NF- 魏 B and its binding to DNA. Hydrocortisone attenuated the p65/DNA binding induced by LPS and inhibited the activation of NF- 魏 B. Pretreatment with TSA or HDAC2si RNA could block the inhibitory effect of hydrocortisone on the activation of NF- 魏 B. Conclusion: HDAC2 is involved in the anti-inflammatory effect of GCs at physiological concentration, and its mechanism is related to the inhibition of NF- 魏 B transcriptional activity mediated by HDAC2.
【作者单位】： 广州医科大学药理教研室;
【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)
【分类号】：R96
本文编号：2366878
[Abstract]:Aim: to investigate the role of histone deacetylase 2 (HDAC2) in anti-inflammatory effects of glucocorticoid (GCs). Methods: lipopolysaccharide (LPS) () was incubated with peritoneal macrophages for 20 mg/L to induce inflammatory response. The levels of TNF- 伪 and IL-1 尾 in the supernatant of cell culture were measured by ELISA method. Western blot and Trans AM NF- 魏 B p65 kit were used to detect the nuclear translocation of NF- 魏 B and the binding activity of NF- 魏 B to DNA. TSA or HDAC2 si RNA, a HDAC blocker, was used to observe the inhibition of LPS induced inflammation by hydrocortisone on the physiological concentration of HDAC2. The reaction and the activation of NF- 魏 B. Results: LPS stimulated the production of TNF- 伪 and IL-1 尾 in a concentration-dependent manner. Hydrocortisone inhibited the production of TNF- 伪 and IL-1 尾 in a dose-dependent manner, but was pretreated with TSA or HDAC2 si RNA,. The inhibitory effect of hydrocortisone on TNF- 伪 and IL-1 尾 release induced by LPS was significantly reduced. Further studies showed that LPS significantly induced the nuclear translocation of NF- 魏 B and its binding to DNA. Hydrocortisone attenuated the p65/DNA binding induced by LPS and inhibited the activation of NF- 魏 B. Pretreatment with TSA or HDAC2si RNA could block the inhibitory effect of hydrocortisone on the activation of NF- 魏 B. Conclusion: HDAC2 is involved in the anti-inflammatory effect of GCs at physiological concentration, and its mechanism is related to the inhibition of NF- 魏 B transcriptional activity mediated by HDAC2.
【作者单位】： 广州医科大学药理教研室;
【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)
【分类号】：R96
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