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.
- Resource Type
- Article
- Authors
- Chen, Xi; Guan, Xiao-jun; Peng, Xiao-hua; Cui, Zhi-lei; Luan, Chun-yu; Guo, Xue-jun
- Source
- Inflammation Research. Jul2015, Vol. 64 Issue 7, p513-526. 14p.
- Subject
- *ACETYLATION
*LYSINE
*HISTONES
*PHYSIOLOGICAL effects of tobacco
*LABORATORY rats
*OBSTRUCTIVE lung disease diagnosis
- Language
- ISSN
- 1023-3830
Objective and design: Cigarette 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. Methods: Sprague-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. Results: CS 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. Conclusions: CS 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. [ABSTRACT FROM AUTHOR]