title: Hypomethylation of perforin regulatory elements in CD4+ T cells from rat spleens contributes to the development of autoimmune emphysema.
abstract: OBJECTIVE
  It is widely accepted that perforin regulatory elements are hypomethylated in CD4+ T cells from patients with active lupus, but whether this is the case in autoimmune emphysema is not known.
  
  
  METHODS
  Twenty rats were randomly divided into a normal control group and an emphysema group. Rat models of emphysema were established by intraperitoneal injection with xenogeneic endothelial cells. The levels of tumour necrosis factor-α, interleukin-8 and matrix metalloproteinase (MMP)-9 in bronchoalveolar lavage fluid (BALF) were measured, lung mean linear intercept and destructive index measured. Mean methylation of perforin gene promoter in CD4+ T cells and the expression of perforin were investigated. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling methods were used to examine the percentage of apoptotic cells in the alveolar septa.
  
  
  RESULTS
  The levels of MMP-9 in BALF were higher in emphysema group than in control group (P < 0.05). The mean linear intercept and destructive index were higher in emphysema group than in control group (P < 0.05). The mean perforin gene promotor methylation of emphysema group was significantly decreased as compared with control group, while the expression levels of perforin gene were relatively higher (P < 0.05). There were more terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling-positive cells in the alveolar septa in control group than in emphysema group.
  
  
  CONCLUSIONS
  Hypomethylation of perforin regulatory elements in CD4+ T cells may result in the lung septal cell apoptosis associated with the development of experimental autoimmune emphysema. MMP-9 may play an important role in the pathogenesis of this kind of disease.
authors: Department of Respiratory Medicine, Guizhou Provincial People's Hospital, Guiyang, Guizhou, China.
authors: Cheng
authors: C
authors: Zhang
authors: Mu-Yun
authors: MY
authors: Yan
authors: Ping
authors: P
authors: Lu
authors: Ping
authors: P
authors: Chen
authors: Min
authors: M
authors: Yang
authors: Xian-Wei
authors: XW
authors: Ye
authors: Mei
authors: M
authors: Xu
authors: Zhang-Hong Ou
authors: ZH
authors: Yang
authors: Xiang-Yan
authors: XY
authors: Zhang
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics* / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D018929:Cell Culture Techniques; D019175:DNA Methylation; D004195:Disease Models, Animal; D020287:In Situ Nick-End Labeling; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D052899:Pore Forming Cytotoxic Proteins / Q000235:genetics* / Q000378:metabolism; D011656:Pulmonary Emphysema / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D050436:Regulatory Elements, Transcriptional / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013154:Spleen / Q000166:cytology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016209:Interleukin-8; D052899:Pore Forming Cytotoxic Proteins; D014409:Tumor Necrosis Factor-alpha; C510465:perforin, rat; D020780:Matrix Metalloproteinase 9
keywords: CD4+ T cell; autoimmune emphysema; hypomethylation; perforin regulatory element; rat