{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T12:11:20Z","timestamp":1780056680089,"version":"3.54.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2011,7,1]],"date-time":"2011-07-01T00:00:00Z","timestamp":1309478400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>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-\u03b1. We also found that A. fumigatus extracts activated the TNF-\u03b1\u2013converting enzyme (TACE), critical for the cleavage of membrane-bound pro\u2013TGF-\u03b1, and its inhibition with low-molecular weight inhibitors or small interfering RNA suppressed the expression of MUC5AC. The protease activity of A. fumigatus extracts was greater than that of other fungal extracts, and treatment with a serine protease inhibitor, but not with a cysteine protease inhibitor, eliminated its ability to activate TACE or induce the expression of MUC5AC mRNA in NCI-H292. In conclusion, the prominent serine protease activity of A. fumigatus, which caused the overproduction of mucus by the bronchial epithelium via the activation of the TACE\/TGF-\u03b1\/epidermal growth factor receptor pathway, may be a pathogenetic mechanism of allergic bronchopulmonary mycosis.<\/jats:p>","DOI":"10.4049\/jimmunol.1002257","type":"journal-article","created":{"date-parts":[[2011,6,18]],"date-time":"2011-06-18T04:18:20Z","timestamp":1308370700000},"page":"999-1005","source":"Crossref","is-referenced-by-count":52,"title":["Induction of Mucin and MUC5AC Expression by the Protease Activity of <i>Aspergillus fumigatus<\/i> in Airway Epithelial Cells"],"prefix":"10.1093","volume":"187","author":[{"given":"Tsuyoshi","family":"Oguma","sequence":"first","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine , Tokyo 160-8582 ,","place":["Japan"]},{"name":"Kawasaki Municipal Hospital , Kawasaki 210-0013 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Medicine, Department of Medicine, Keio University School of Medicine , Tokyo 160-8582 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuya","family":"Shiomi","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine , Tokyo 160-8582 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nao","family":"Ohmori","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine , Tokyo 160-8582 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soichiro","family":"Ueda","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine , Tokyo 160-8582 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Department of Medicine, Keio University School of Medicine , Tokyo 160-8582 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukikazu","family":"Natori","sequence":"additional","affiliation":[{"name":"RNAi Co., Ltd. , Tokyo 113-0033 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig M","family":"Lilly","sequence":"additional","affiliation":[{"name":"Pulmonary, Allergy, and Critical Care Division, Department of Medicine, University of Massachusetts , Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuo","family":"Satoh","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Gene Diagnosis, Institute of Medical Mycology and Genome Research Center, Graduate School of Medical Science, Teikyo University , Tokyo 192-0394 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