RT Journal Article
SR Electronic
T1 Primary human lung fibroblasts of asthma patients proliferate significantly faster than those of controls in response to muscarinic receptor stimulation with carbachol
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P525
VO 42
IS Suppl 57
A1 Luigi Costa
A1 Michael Roth
A1 Michael Tamm
A1 Pieter Borger
YR 2013
UL http://erj.ersjournals.com/content/42/Suppl_57/P525.abstract
AB Background: Several chronic inflammatory lung diseases are associated with airway remodeling involving pulmonary lung fibroblasts. Although the both platelet-derived growth factor (PDGF)-beta receptor and the muscarinic receptor signaling system has been implicated in the remodeling process, their interaction is not well defined in lung fibroblasts.Objective: Here we investigated the role of PDGF-BB and of muscarinic receptors with respect to proliferation of human primary airway fibroblasts.Methods: Fibroblasts were isolated from asthmatic (n=8) and non-asthmatic subjects (n=8). Cells were stimulated with PDGF-BB (5, 10ng/ml), carbachol (10-6M, 10-5M), or the combination of PDGF-BB (5ng/ml) and carbachol (10-6M) for 3 and 5 days.Results: PDGF-BB alone significantly increased the proliferation of fibroblasts from both asthma and non-asthma patients in a dose-dependent manner, while carbachol alone had no effect. In combination, carbachol significantly increased PDGF-BB induced proliferation of fibroblasts. Importantly, the enhancing effect of carbachol on PDGF-BB-induced fibroblast proliferation was significantly stronger in cells obtained from asthma patient compared to cells of non-asthma subjects.Conclusion: Muscarinic receptor activation alone is insufficient to induce fibroblast proliferation, while it potentiates the mitogenic effect of PDGF-BB especially in asthmatic lung fibroblasts. This observation may in part explain the pathologic increase of the sub-epithelial mesenchymal cell layer in asthma patients.