陈小萍,李明慧,从美丽,康雁君,郭文平,张永振.SIRT1抑制细菌脂多糖耐受THP-1细胞中IL-1βmRNA的转录[J].Chinese journal of Epidemiology,2011,32(6):613-616 |
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 lipopotysaccharide tolerant THP-1 cells |
Received:January 28, 2011 |
DOI: |
KeyWord: 沉默信息调节因子1 IL-1β启动子 组蛋白乙酰化 |
English Key Word: Silent information regulation 2 homolog 1 IL-1β promoter Histone acetylation |
FundProject: |
Author Name | Affiliation | E-mail | CHEN Xiao-ping | State Key Laboratory for Infectious Disease Control and Prevention, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China | | LI Ming-hui | State Key Laboratory for Infectious Disease Control and Prevention, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China | | CONG Mei-li | State Key Laboratory for Infectious Disease Control and Prevention, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China | | KANG Yan-jun | State Key Laboratory for Infectious Disease Control and Prevention, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China | | GUO Wen-ping | State Key Laboratory for Infectious Disease Control and Prevention, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China | | ZHANG Yong-zhen | State Key Laboratory for Infectious Disease Control and Prevention, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China | yongzhenzhang@sohu.com |
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Abstract: |
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(SIRTI)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-time PCR定量研究1L-1β启动子区SIRT1结合情况和组蛋白H3lys9/H4lys16的乙酰化情况.结果 在LPS耐受的THP-1细胞中,SIRTI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H3 lys9/H4 lys16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H3 lys9/H4lys 16乙酰化的增加(P<0.05).然而,正常细胞和耐受细胞p65 lys310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-113mRNA的转录,其作用与p65 lys310乙酰化无关,但是与IL-1β启动子区乙酰化有关. |
English Abstract: |
Objective To explore the role of silent information regulation 2 homolog 1 (SIRTl) in the regulation of IL-lβ 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-timePCR were applied to quantify the binding of SIRTl and histone H3 lys9/H4 lysl6 acetylation to IL-1β promoter. IL-1β mRNA transcription was studied after knocking down the SIRTl. Results Thebinding of SIRTl 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 lysl6 acetylation (P<0.05, compared with normal cells). Knocking-down of SIRTl 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 lysl6 acetylation (P<0.05). However,there was no significant difference of p65 lys310 acetylation between normal and tolerant cells. Conclusion SIRTl inhibited the IL-1 β mRNA transcription in tolerant THP-1 cells but had not related to p65 lys310 acetylation. However, it was related to IL-1 p promoter acetylation. |
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