title: Overexpression of RAGE contributes to cigarette smoke-induced nitric oxide generation in COPD.
abstract: BACKGROUND
  Receptor for advanced glycation end products (RAGE), a multiple-ligands receptor, is implicated in chronic obstructive pulmonary disease (COPD). This study was designed to investigate the potential role of RAGE in nitric oxide (NO) generation, an endogenous marker of nitrosative stress in COPD.
  
  
  METHODS
  Lung tissues from COPD patients were used to describe the relationship between RAGE expression and NO level. RAGE expression was assessed by immunohistochemistry, western blot, and ELISA. Human bronchial epithelial cells (16HBE) were cultured with cigarette smoke extract (CSE). Neutralizing antibody against RAGE was used to detect the role of RAGE in CSE-induced NO generation by 16HBE cells.
  
  
  RESULTS
  Compared with nonsmoker controls, overexpression of RAGE was significantly detected in COPD smokers (p < 0.01), but not healthy smokers and nonsmokers with COPD, which was dominantly expressed at bronchiolar epithelia. Correlation analysis showed that RAGE in COPD smokers was positively related to NO level, smoking status, and lung function decline. In cultured 16HBE cells treated with CSE, soluble RAGE was reduced; however, full-length RAGE was enhanced significantly as the same trend as NO generation. Moreover, increased NO level and NO synthase activity, decreased total glutathione (a major cellular antioxidant), enhanced nuclear translocation of p65 (a key molecule of nuclear factor (NF)-κB) and release of NF-κB-dependent proinflammatory cytokines were all reversed by pretreatment of anti-RAGE antibody.
  
  
  CONCLUSIONS
  These findings suggest that overexpression of RAGE contributes to CS-induced NO generation in COPD with involvement in NF-κB activation.
authors.affiliation: Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, 610041, Sichuan, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Lingli
authors.initials: L
authors.lastname: Guo
authors.forename: Yongchun
authors.initials: Y
authors.lastname: Shen
authors.forename: Ting
authors.initials: T
authors.lastname: Yang
authors.forename: Chun
authors.initials: C
authors.lastname: Wan
authors.forename: Zenglin
authors.initials: Z
authors.lastname: Liao
authors.forename: Dan
authors.initials: D
authors.lastname: Xu
authors.forename: Fuqiang
authors.initials: F
authors.lastname: Wen
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*; D015398:Signal Transduction; D012907:Smoking / Q000009:adverse effects*; D051996:Transcription Factor RelA / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C498143:RELA protein, human; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D051996:Transcription Factor RelA; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D005978:Glutathione