RT Journal Article
SR Electronic
T1 Injury and repair responses of parenchymal fibroblasts in advanced chronic obstructive pulmonary disease
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P1847
VO 44
IS Suppl 58
A1 Green, Nicola J.
A1 Lagan, Anna
A1 Walker, Andrew
A1 Jenkins, Gisli
A1 Johnson, Simon
A1 Finch, Donna K.
A1 Knox, Alan
A1 Fisher, Andrew J.
A1  COPDMAP Study
YR 2014
UL https://publications.ersnet.org//content/44/Suppl_58/P1847.abstract
AB BackgroundCOPD exacerbations contribute to progressive disease by inducing acute on chronic inflammation. Leukocytes have traditionally been considered orchestrators of this inflammation. We hypothesise tissue injury and release of damage associated molecular patterns(DAMPs) such as IL-1α drive inflammation and dysfunctional repair in parenchymal lung fibroblasts.MethodsLung fibroblasts were cultured from control(n=6) and COPD(n=6 GOLD stage III/IV) lung tissue. Cells were stimulated with Interleukin- 1alpha(IL1α) or Tissue Growth Factor- beta(TGFβ). Smad2 phosporylation(ELISA) was measured at 1hr and pro-inflammatory cytokine concentrations(multiplex MSD) and MMP2 activity(zymography) in supernatants measured at 24hr.ResultsIL1α induced a dose dependent increase in inflammatory cytokines(IL6,IL8, IL1β, GM-CSF and TNFα) from both control and COPD fibroblasts. The COPD fibroblasts demonstrated a more dramatic response to IL1α than controls. Constitutive Smad2 phosphorylation was higher in control than COPD fibroblasts and increased further in response to TGFβ stimulation. This increase was attenuated in COPD fibroblasts. MMP2 activity was detected in both control and COPD fibroblasts with no additional response to either TGFβ or IL1α stimulation.ConclusionLung fibroblasts respond to the DAMP IL1α, adopting a potent pro-inflammatory phenotype a response which is exaggerated in COPD. In addition, COPD fibroblasts have a blunted signalling response to TGFβ compared to controls. These preliminary observations suggest COPD fibroblasts adopt a pro-inflammatory phenotype with reduced repair capacity in response to tissue injury implicating them in the pathophysiology of the disease.