Pro-inflammatory phenotype of COPD fibroblasts not compatible with repair in COPD lung

J Cell Mol Med. 2012 Jul;16(7):1522-32. doi: 10.1111/j.1582-4934.2011.01492.x.


Chronic obstructive pulmonary disease (COPD) is characterized by loss of elastic fibres from small airways and alveolar walls, with the decrease in elastin increasing with disease severity. It is unclear why there is a lack of repair of elastic fibres. We have examined fibroblasts cultured from lung tissue from subjects with or without COPD to determine if the secretory profile explains lack of tissue repair. In this study, fibroblasts were cultured from lung parenchyma of patients with mild COPD [Global initiative for chronic Obstructive Lung Disease (GOLD) 1, n= 5], moderate to severe COPD (GOLD 2-3, n= 12) and controls (non-COPD, n= 5). Measurements were made of proliferation, senescence-associated β-galactosidase-1, mRNA expression of IL-6, IL-8, MMP-1, tropoelastin and versican, and protein levels for IL-6, IL-8, PGE(2,) tropoelastin, insoluble elastin, and versican. GOLD 2-3 fibroblasts proliferated more slowly (P < 0.01), had higher levels of senescence-associated β-galactosidase-1 (P < 0.001) than controls and showed significant increases in mRNA and/or protein for IL-6 (P < 0.05), IL-8 (P < 0.01), MMP-1 (P < 0.05), PGE(2) (P < 0.05), versican (P < 0.05) and tropoelastin (P < 0.05). mRNA expression and/or protein levels of tropoelastin (P < 0.01), versican (P < 0.05), IL-6 (P < 0.05) and IL-8 (P < 0.05) were negatively correlated with FEV1% of predicted. Insoluble elastin was not increased. In summary, fibroblasts from moderate to severe COPD subjects display a secretory phenotype with up-regulation of inflammatory molecules including the matrix proteoglycan versican, and increased soluble, but not insoluble, elastin. Versican inhibits assembly of tropoelastin into insoluble elastin and we conclude that the pro-inflammatory phenotype of COPD fibroblasts is not compatible with repair of elastic fibres.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cell Proliferation*
  • Female
  • Fibroblasts / cytology*
  • Fibroblasts / metabolism
  • Humans
  • Inflammation / genetics*
  • Inflammation / physiopathology
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism
  • Lung / physiopathology*
  • Male
  • Middle Aged
  • Phenotype
  • Pulmonary Disease, Chronic Obstructive / genetics*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Real-Time Polymerase Chain Reaction
  • Tropoelastin / genetics
  • Tropoelastin / metabolism
  • Up-Regulation
  • Versicans / genetics
  • Versicans / metabolism
  • Wound Healing
  • beta-Galactosidase / genetics
  • beta-Galactosidase / metabolism


  • Interleukin-6
  • Interleukin-8
  • Tropoelastin
  • Versicans
  • beta-Galactosidase