红霉素上调组蛋白去乙酰化酶2表达减轻氧化应激下THP-1细胞的糖皮质激素抵抗

发布时间：2018-06-26 13:00

本文选题：红霉素 + 氧化应激　；参考：《细胞与分子免疫学杂志》2014年04期

【摘要】：目的探讨红霉素(EM)对氧化应激下人THP-1单核细胞糖皮质激素抵抗的作用及机制。方法 EM预孵育THP-1细胞后予烟草烟雾提取物(CSE)刺激细胞,用质粒脂质体法将构建好的组蛋白去乙酰化酶2沉默RNA(HDAC2-siRNA)转染细胞,ELISA检测细胞培养上清白细胞介素8(IL-8)的含量,实时荧光定量PCR(qRT-PCR)和Western blot法分析HDAC2表达情况。结果 EM组的IL-8抑制率明显高于CSE组,而低于对照组(P0.05),EM组地塞米松半数抑制浓度(IC50-Dex)低于CSE组,而高于对照组(P0.05)。EM组HDAC2蛋白的表达高于CSE组,而低于对照组(P0.05)。除此之外,应用HDAC2-siRNA转染细胞后HDAC2 mRNA及HDAC2蛋白的表达均明显低于对照组及空转组,而加用EM后其表达明显升高(P0.05)。结论 CSE刺激下的THP-1细胞对地塞米松的敏感性明显降低,EM可通过上调HDAC2蛋白的表达减轻氧化应激下THP-1细胞的糖皮质激素抵抗。
[Abstract]:Objective to investigate the effect and mechanism of erythromycin (EM) on glucocorticoid resistance of human THP-1 monocytes under oxidative stress. Methods THP-1 cells were preincubated with EM and stimulated by tobacco smoke extract (CSE). The constructed histone deacetylase 2 silencing RNA (HDAC2-siRNA) transfected cells were transfected with HDAC2-siRNA to detect the interleukin-8 (IL-8) content in the supernatant by plasmid liposome method. The expression of HDAC2 was analyzed by real time quantitative PCR (qRT-PCR) and Western blot. Results the inhibition rate of IL-8 in EM group was significantly higher than that in CSE group, but lower than that in control group (P0.05). IC50-Dex in EM group was lower than that in CSE group, while the expression of HDAC2 protein in EM group was higher than that in CSE group (P0.05), but lower than that in control group (P0.05). In addition, the expression of HDAC2 mRNA and HDAC2 protein in HDAC2-siRNA transfected cells were significantly lower than those in control group and empty group, but the expression of HDAC2 mRNA and HDAC2 protein were significantly increased after treatment with EM (P0.05). Conclusion the sensitivity of THP-1 cells stimulated by CSE to dexamethasone is significantly reduced by up-regulating the expression of HDAC2 protein to alleviate the glucocorticoid resistance of THP-1 cells under oxidative stress.
【作者单位】：广西医科大学第一附属医院呼吸内科;广西医科大学第一附属医院内科ICU;
【基金】：国家自然科学基金(81260012,81160009)
【分类号】：R563.9

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