SIRT1抑制细菌脂多糖耐受THP-1细胞中IL-1βmRNA的转录  

SIRT1 inhibits IL-1β mRNA transcription in lipopolysaccharide tolerant THP-1 cells

作　　者：陈小萍[1] 李明慧[1] 从美丽[1] 康雁君[1] 郭文平[1] 张永振[1] 

机构地区：[1]中国疾病预防控制中心传染病预防控制所传染病预防控制国家重点实验室,北京102206

出　　处：《中华流行病学杂志》2011年第6期613-616,共4页Chinese Journal of Epidemiology

摘　　要：目的研究细菌脂多糖（LPS）耐受的THP-1细胞中沉默信息调节因子1（SIRTl）对IL-1β转录的调节作用。方法使用LPS耐受的人单核细胞THP-1模型，染色体免疫沉淀和real-timePCR定量研究IL-1β启动子区SIRT1结合情况和组蛋白H3lys9／H4lysl6的乙酰化情况。结果在LPS耐受的THP～1细胞中，SIRT1对IL-1β启动子区的结合增加约5倍左右（P〈0．05），同时伴随着组蛋白H3lys9／H4lysl6乙酰化的低水平状态（与正常细胞相比P〈0．05）。SIRT1沉默使IL-1β的转录恢复到正常细胞的68％（P〈0．05），同时伴随着组蛋白H3lys9／H4lysl6乙酰化的增加（P〈0．05）。然而，正常细胞和耐受细胞p65lys310乙酰化水平无明显差异。结论SIRT1抑制LPS耐受的THP—1细胞中IL-1βmRNA的转录，其作用与p65lys310乙酰化无关，但是与IL-1β启动子区乙酰化有关。Objective To explore the role of silent information regulation 2 homolog 1 （SIRT1） in the regulation of IL-1 β mRNA transcription in lipopolysaccharide （LPS） tolerant THP-1 cells. Methods THP-1 human promonocyte model of endotoxin tolerance that simulates the sepsis leukocyte phenotype was used. Chromatin immunoprecipitation assay （CHIP） and real-time PCR were applied to quantify the binding of SIRT1 and histone H3 lys9/H4 lysl6 acetylation to IL-1β promoter. IL-1 β mRNA transcription was studied after knocking down the SIRT1. Results The binding of SIRT1 to IL-1 β promoter increased about 5 times in tolerant THP-1 cells （P〈0.05）, which was accompanied by the low level of histone H3 lys9/H4 lysl6 acetylation （P〈0.05, compared with normal cells）. Knocking-down of SIRT1 increased the transcription of IL-1 β mRNA up to the level of 68% of normal cells （P〈0.05）, which was accompanied by the increase of histone H3 lys9/H4 lysl 6 acetylation （P〈0.05）. However, there was no significant difference of p65 lys310 acetylation between normal and tolerant cells. Conclusion SIRT1 inhibited the IL-1 β mRNA transcription in tolerant THP-1 ceils but had not related to p65 lys310 acetylation. However, it was related to IL-1β promoter acetylation.

关 键 词：沉默信息调节因子1 IL-1β启动子 组蛋白乙酰化 

分 类 号：R363[医药卫生—病理学]