TY - JOUR 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 VL - 42 IS - Suppl 57 SP - P525 AU - Luigi Costa AU - Michael Roth AU - Michael Tamm AU - Pieter Borger Y1 - 2013/09/01 UR - http://erj.ersjournals.com/content/42/Suppl_57/P525.abstract N2 - 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. ER -