title: 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.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Respirology Medicine, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200092, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Xiao-jun
authors.initials: XJ
authors.lastname: Guan
authors.forename: Xiao-hua
authors.initials: XH
authors.lastname: Peng
authors.forename: Zhi-lei
authors.initials: ZL
authors.lastname: Cui
authors.forename: Chun-yu
authors.initials: CY
authors.lastname: Luan
authors.forename: Xue-jun
authors.initials: XJ
authors.lastname: Guo
mesh_terms: D000107:Acetylation; D000818:Animals; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics; D016207:Cytokines / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D056284:Histone Deacetylase 1 / Q000096:biosynthesis* / Q000235:genetics; D006657:Histones / Q000737:chemistry*; D019570:Inhalation Exposure / Q000009:adverse effects; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008239:Lysine / Q000737:chemistry*; D008264:Macrophages / Q000187:drug effects; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D000067996:RAW 264.7 Cells / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D016207:Cytokines; D006657:Histones; D016209:Interleukin-8; D012906:Smoke; D014409:Tumor Necrosis Factor-alpha; D020780:Matrix Metalloproteinase 9; C515890:Hdac1 protein, rat; D056284:Histone Deacetylase 1; D008239:Lysine