PROTEASES FROM ASPERGILLUS-FUMIGATUS INDUCE RELEASE OF PROINFLAMMATORY CYTOKINES AND CELL DETACHMENT IN AIRWAY EPITHELIAL-CELL LINES

Aspergillus fumigatus is a pathogen causing; diverse respiratory disor ders, Several studies have suggested that fungal proteases may play a role in the pathogenicity of fungi, Since the airways are the most com mon route for entry of. A, fumigatus, this study focused on the abilit y of fungal proteases to induce the release of proinflammatory cytokin es and to cause cell detachment in human pulmonary epithelial cell Lin es. It was shown that fungal serine protease activity induced the prod uction of interleukin (IL)-8 and IL-6 and monocyte chemotactic protein -1 and caused cell detachment in a dose-dependent fashion. Chymostatin , antipain, phenylmethylsulfonyl fluoride, and heat treatment complete ly inhibited fungal protease activity, cytokine production and cell de tachment; antileukoprotease partially inhibited these activities. By c ausing cell detachment, fungal proteases may decrease the physical bar rier function of the epithelium, however, by eliciting a cytokine resp onse, the epithelium may signal the mucosal inflammatory response agai nst A, fumigatus.