【摘要】：目的:探討組蛋白去乙�；�2(HDAC2)在生理濃度的糖皮質(zhì)激素(GCs)抗炎效應(yīng)中的作用。方法:脂多糖(LPS)(20 mg/L)孵育腹腔巨噬細(xì)胞誘導(dǎo)炎癥反應(yīng)。ELISA法測定細(xì)胞培養(yǎng)上清中炎癥因子TNF-α和IL-1β水平;Western blot及Trans AM NF-κB p65試劑盒檢測NF-κB核轉(zhuǎn)位和NF-κB與DNA的結(jié)合活性。HDAC阻斷劑TSA或HDAC2 si RNA用于觀察抑制HDAC2活性后對生理濃度的氫化可的松抑制LPS誘導(dǎo)的炎癥反應(yīng)及NF-κB活化的影響。結(jié)果 :LPS濃度依賴性的刺激TNF-α、IL-1β的產(chǎn)生,生理濃度的氫化可的松對此有明顯的抑制作用,而預(yù)先給予TSA或HDAC2 si RNA,明顯減弱氫化可的松對LPS誘導(dǎo)的TNF-α和IL-1β釋放的抑制作用。進(jìn)一步研究顯示,LPS明顯誘導(dǎo)NF-κB的核轉(zhuǎn)位及與DNA的結(jié)合。生理濃度的氫化可的松減弱LPS誘導(dǎo)的p65/DNA結(jié)合從而抑制NF-κB的活化過程。預(yù)先給予TSA或HDAC2si RNA則可以阻斷氫化可的松對NF-κB活化的抑制作用。結(jié)論 :HDAC2參與了生理濃度的GCs的抗炎效應(yīng),其機(jī)制與HDAC2介導(dǎo)的NF-κB轉(zhuǎn)錄活性的抑制有關(guān)。
[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- 偽 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- 偽 and IL-1 尾 in a concentration-dependent manner. Hydrocortisone inhibited the production of TNF- 偽 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- 偽 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.
【作者單位】： 廣州醫(yī)科大學(xué)藥理教研室;
【基金】：廣東省自然科學(xué)基金資助項目(編號:2016A030313569) 廣州市教育局基金資助項目(編號:10A179)
【分類號】：R96

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