Abstract:Objective:To investigate the effects of Aspergillus fumigatus extract (AFE) on the expression of GM-CSF in human bronchial epithelial cells and its possible mechanism.Methods: Human bronchial epithelial cells (16HBE-14o) were cultured in vitro and were exposed to different concentrations of AFE (0,8,16 and 20 mg/L) for different peroids (12、24、48、72 h).Moreover,heat-treated AFE,serine protease inhibitors (aprotinin),protease-activated receptor-2 (PAR-2) agonist (SLIGLV- NH2) and PAR-2 antagonist (FSLLRY-NH2) were also used to treat 16HBE-14o cells.The production and release of GM-CSF in different supernatants was determined by ELISA.The expression of GM-CSF mRNA was measured by RT-PCR.Results: 16HBE-14o cells in the normal control group only had slight expression of GM-CSF; the expression was significantly increased after AFE treatment(P<0.01); and the effect of AFE was in a time- and dose-dependent manner.PAR-2 agonist also promoted release of GM-CSF.Aprotinin and PAR-2 antagonist (FSLLRY-NH2) almost totally inhibited the effect of AFE on GM-CSF production by 16HBE-14o cells.Heat-treated AFE,which lost protease activities,exerted no effect on GM-CSF production.Conclusion: AFE,with its protease activity,can activate PAR-2,and subsequently causes GM-CSF synthesis and release by airway epithelial cells,which may contribute to the development and deterioration of asthma.