Chen Xiao-ping, Li Ming-hui, Cong Mei-li, Kang Yan-jun, Guo Wen-ping, Zhang Yong-zhen
National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
Zhonghua Liu Xing Bing Xue Za Zhi. 2011 Jun;32(6):613-6.
To explore the role of silent information regulation 2 homolog 1 (SIRT1) in the regulation of IL-1β mRNA transcription in lipopolysaccharide (LPS) tolerant THP-1 cells.
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 lys16 acetylation to IL-1β promoter. IL-1β mRNA transcription was studied after knocking down the SIRT1.
The binding of SIRT1 to IL-1β 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 lys16 acetylation (P < 0.05, compared with normal cells). Knocking-down of SIRT1 increased the transcription of IL-1β mRNA up to the level of 68% of normal cells (P < 0.05), which was accompanied by the increase of histone H3 lys9/H4 lys16 acetylation (P < 0.05). However, there was no significant difference of p65 lys310 acetylation between normal and tolerant cells.
SIRT1 inhibited the IL-1β mRNA transcription in tolerant THP-1 cells but had not related to p65 lys310 acetylation. However, it was related to IL-1β promoter acetylation.
探讨沉默信息调节因子2同源物1（SIRT1）在脂多糖（LPS）耐受的THP-1细胞中对白细胞介素-1β（IL-1β）mRNA转录的调控作用。
采用模拟脓毒症白细胞表型的THP-1人原单核细胞内毒素耐受模型。应用染色质免疫沉淀分析（ChIP）和实时荧光定量PCR检测SIRT1与组蛋白H3赖氨酸9/组蛋白H4赖氨酸16乙酰化与IL-1β启动子的结合情况。在敲低SIRT1后研究IL-1β mRNA的转录情况。
在耐受的THP-1细胞中，SIRT1与IL-1β启动子的结合增加了约5倍（P<0.05），同时伴随着组蛋白H3赖氨酸9/组蛋白H4赖氨酸16乙酰化水平降低（与正常细胞相比，P<0.05）。敲低SIRT1后，IL-1β mRNA转录增加，达到正常细胞水平的68%（P<0.05），同时伴随着组蛋白H3赖氨酸9/组蛋白H4赖氨酸16乙酰化增加（P<0.05）。然而，正常细胞与耐受细胞之间p65赖氨酸310乙酰化无显著差异。
SIRT1抑制耐受的THP-1细胞中IL-1β mRNA转录，且与p65赖氨酸310乙酰化无关，但与IL-1β启动子乙酰化有关。
