title: Proteases from Aspergillus fumigatus induce release of proinflammatory cytokines and cell detachment in airway epithelial cell lines.
abstract: Aspergillus fumigatus is a pathogen causing diverse respiratory disorders. Several studies have suggested that fungal proteases may play a role in the pathogenicity of fungi. Since the airways are the most common route for entry of A. fumigatus, this study focused on the ability of fungal proteases to induce the release of proinflammatory cytokines and to cause cell detachment in human pulmonary epithelial cell lines. It was shown that fungal serine protease activity induced the production 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 completely inhibited fungal protease activity, cytokine production and cell detachment; antileukoprotease partially inhibited these activities. By causing cell detachment, fungal proteases may decrease the physical barrier function of the epithelium; however, by eliciting a cytokine response, the epithelium may signal the mucosal inflammatory response against A. fumigatus.
authors.affiliation: Department of Allergology, University Hospital Groningen, Netherlands.
authors.forename: J F
authors.initials: JF
authors.lastname: Tomee
authors.forename: A T
authors.initials: AT
authors.lastname: Wierenga
authors.forename: P S
authors.initials: PS
authors.lastname: Hiemstra
authors.forename: H K
authors.initials: HK
authors.lastname: Kauffman
mesh_terms: D001232:Aspergillus fumigatus / Q000201:enzymology*; D001980:Bronchi / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D010450:Endopeptidases / Q000502:physiology*; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D006358:Hot Temperature; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D016209:Interleukin-8; D015842:Serine Proteinase Inhibitors; D010450:Endopeptidases