Acetylation of lysine 9 on histone H3 is associated with increased pro-inflammatory cytokine release in a cigarette smoke-induced rat model through HDAC1 depression
Acetylation of lysine 9 on histone H3 is associated with increased pro-inflammatory cytokine release in a cigarette smoke-induced rat model through HDAC1 depression
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DOI：
10.1007/s00011-015-0832-y
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发表时间：
2015-06
影响因子：
6.7
通讯作者：
Xi Chen;X. Guan;Xiaohong Peng;Zhi-lei Cui;C-Y. Luan;Xue-Jun Guo
中科院分区：
文献类型：
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作者：
Xi Chen;X. Guan;Xiaohong Peng;Zhi-lei Cui;C-Y. Luan;Xue-Jun Guo
目的与设计香烟烟雾(CS)诱导的炎症在慢性阻塞性肺疾病(COPD)中起重要作用。然而，组蛋白3赖氨酸9(H3K9)乙酰化在COPD炎症中的作用尚不清楚。本研究评价了H3K9乙酰化对大鼠肺和巨噬细胞转录的影响。方法SD大鼠暴露于CS 6周或12周，收集肺组织。结果香烟烟雾提取物作用6周和12周后，大鼠肺组织中单核细胞趋化蛋白-1和白细胞介素8的基因和蛋白表达均增加，而肿瘤坏死因子-α和基质金属蛋白酶9的表达仅在12周后才开始增加。CSE暴露48小时后，巨噬细胞中这些基因的表达增加。大鼠肺和巨噬细胞中乙酰化H3K9蛋白的丰度增加与组蛋白脱乙酰酶-1(HDAC1)的表达减少有关。染色质免疫沉淀显示，在体内和体外，这些基因启动子区域的乙酰化H3K9水平都增加了。结论CS通过抑制HDAC1诱导的大鼠肺和巨噬细胞H3K9乙酰化，进而改变促炎介质和蛋白水解酶基因的表达。
Objective and designCigarette smoke (CS)-induced inflammation is critical in chronic obstructive pulmonary disease (COPD). However, the role of acetylation at histone 3 lysine 9 (H3K9) in COPD inflammation remains unclear. The present study assessed the effect of acetylation of H3K9 on transcription both in rat lungs and in macrophages.MethodsSprague–Dawley rats were exposed to CS for either 6 or 12 weeks and rat lungs were collected. Rat macrophages were subjected to 20 % cigarette smoke extract (CSE) for 48 h.ResultsCS increased MCP-1 and IL-8 expressions at both mRNA and protein levels in rat lungs after 6 and 12 weeks; increased TNF-α and MMP9 expressions at both levels were noted only after 12 weeks. CSE increased these genes expression in macrophages after 48 h exposure. Increased abundance of acetylated H3K9 protein in rat lungs and in macrophages were associated with decreased expression of histone deacetylase-1(HDAC1). Chromatin immunoprecipitation demonstrated increased level of acetylated H3K9 on promoter regions of these genes both in vivo and in vitro. Knockdown of HDAC1 increased these genes mRNA expression.ConclusionsCS increased H3K9 acetylation and subsequently altered the expression of pro-inflammatory mediators and protease genes through HDAC1 depression in CS-induced rat lungs and in macrophages.