title: Alveolar cell senescence exacerbates pulmonary inflammation in patients with chronic obstructive pulmonary disease.
abstract: BACKGROUND
  Alveolar cell senescence is accelerated in patients with chronic obstructive pulmonary disease (COPD).
  
  
  OBJECTIVE
  We tested the hypothesis that alveolar cell senescence contributes to the chronic inflammation that affects the lungs of COPD patients.
  
  
  METHODS
  We exposed alveolar type II-like epithelial (A549) cells to a G-quadruplex-interacting telomerase inhibitor in vitro to induce cellular senescence and analyzed the production of proinflammatory cytokines and the activation of NF-kappaB. Human dermal microvascular endothelial cells (HDMECs) were serially passaged to induce replicative senescence. We also immunostained human lung tissue sections obtained from COPD patients, asymptomatic smokers and asymptomatic nonsmokers and examined correlations between type II cell senescence and inflammation.
  
  
  RESULTS
  Senescent A549 cells and HDMECs, whether stimulated with lipopolysaccharide or not, produced greater amounts of IL-6, IL-8 and TNF-alpha, which paralleled NF-kappaB activation, than did presenescent cells. There were positive correlations between the percentages of senescent type II cells that expressed p16(INK4a) and the percentages of type II cells that expressed phosphorylated NF-kappaB. The lung tissue of the COPD patients contained higher percentages of proinflammatory senescent type II cells that co-expressed p16(INK4a) and phosphorylated NF-kappaB than the tissue from asymptomatic smokers and asymptomatic nonsmokers. Higher percentages of p16(INK4a)-positive senescent type II cells than of p16(INK4a)-negative presenescent type II cells were positive for phosphorylated NF-kappaB.
  
  
  CONCLUSIONS
  Senescence of alveolar epithelial cells is associated with functional alterations of the cells to a proinflammatory phenotype and may contribute to the pathogenesis of COPD.
authors.affiliation: First Department of Medicine, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Tsuji
authors.forename: Kazutetsu
authors.initials: K
authors.lastname: Aoshiba
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nagai
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D018929:Cell Culture Techniques; D016922:Cellular Senescence / Q000502:physiology*; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011014:Pneumonia / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D011650:Pulmonary Alveoli / Q000378:metabolism / Q000473:pathology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D012907:Smoking / Q000378:metabolism / Q000473:pathology
chemical_list: D018836:Inflammation Mediators