in Airway Epithelial Aspergillus fumigatus Expression by the Protease Activity of Induction of Mucin and MUC5AC

Allergic bronchopulmonary mycosis, characterized by excessive mucus secretion, airflow limitation, bronchiectasis, and peripheral blood eosinophilia, is predominantly caused by a fungal pathogen, Aspergillus fumigatus . Using DNA microarray analysis of NCI-H292 cells, a human bronchial epithelial cell line, stimulated with fungal extracts from A. fumigatus , Alternaria alternata , or Penicillium notatum , we identified a mucin-related MUC5AC as one of the genes, the expression of which was selectively induced by A. fumigatus . Quantitative RT-PCR, ELISA, and histochemical analyses confirmed an induction of mucin and MUC5AC expression by A. fumigatus extracts or the culture supernatant of live microorganisms in NCI-H292 cells and primary cultures of airway epithelial cells. The expression of MUC5AC induced by A. fumigatus extracts diminished in the presence of neutralizing Abs or of inhibitors of the epidermal growth factor receptor or its ligand, TGF- a . We also found that A. fumigatus extracts activated the TNF- a –converting enzyme (TACE), critical for the cleavage of membrane-bound pro–TGF- a , and its inhibition with low-molecular weight inhibitors or small interfering RNA suppressed the expression of MUC5AC. The protease activity of followed by the Bonferroni multiple comparison test as a post hoc analysis. The concentrations of MUC5AC protein were compared by an unpaired t test. A p value , 0.05 was considered significant.