Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học 'Respiratory Research cung cấp cho các bạn kiến thức về ngành y đề tài: DMF inhibits PDGF-BB induced airway smooth muscle cell proliferation through induction of heme-oxygenase-1. | Seidel et al. Respiratory Research 2010 11 145 http content 11 1 145 RESPIRATORY RESEARCH RESEARCH Open Access DMF inhibits PDGF-BB induced airway smooth muscle cell proliferation through induction of heme-oxygenase-1 Petra Seidel Stephanie Goulet Katrin Hostettler Michael Tamm Michael Roth Abstract Background Airway wall remodelling is an important pathology of asthma. Growth factor induced airway smooth muscle cell ASMC proliferation is thought to be the major cause of airway wall thickening in asthma. Earlier we reported that Dimethylfumarate DMF inhibits platelet-derived growth factor PDGF -BB induced mitogen and stress activated kinase MSK -1 and CREB activity as well as IL-6 secretion by ASMC. In addition DMF altered intracellular glutathione levels and thereby reduced proliferation of other cell types. Methods We investigated the effect of DMF on PDGF-BB induced ASMC proliferation on mitogen activated protein kinase MAPK activation and on heme oxygenase HO -1 expression. ASMC were pre-incubated for 1 hour with DMF and or glutathione ethylester GSH-OEt SB203580 hemin cobalt-protoporphyrin CoPP or siRNA specific to HO-1 before stimulation with PDGF-BB 10 ng ml . Results PDGF-BB induced ASMC proliferation was inhibited in a dose-dependant manner by DMF. PDGF-BB induced the phosphorylation of ERK1 2 and p38 MAPK but not of JNK. DMF enhanced the PDGF-BB induced phosphorylation of p38 MAPK and there by up-regulated the expression of HO-1. HO-1 induction inhibited the proliferative effect of PDGF-BB. HO-1 expression was reversed by GSH-OEt or p38 MAPK inhibition or HO-1 siRNA which all reversed the anti-proliferative effect of DMF. Conclusion Our data indicate that DMF inhibits ASMC proliferation by reducing the intracellular GSH level with subsequent activation of p38 MAPK and induction of HO-1. Thus DMF might reduce ASMC and airway remodelling processes in asthma. Background Asthma is a chronic inflammatory disease of the airways that is
