Induction of Mucin and MUC5AC expression by the protease activity of aspergillus fumigatus in airway epithelial cells

Tsuyoshi Oguma, Koichiro Asano, Katsuyoshi Tomomatsu, Motohiro Kodama, Koichi Fukunaga, Tetsuya Shiomi, Nao Ohmori, Soichiro Ueda, Takahisa Takihara, Yoshiki Shiraishi, Koichi Sayama, Shizuko Kagawa, Yukikazu Natori, Craig M. Lilly, Kazuo Satoh, Koichi Makimura, Akitoshi Ishizaka

研究成果: Article査読

33 被引用数 (Scopus)

抄録

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 NCIH292 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-α. We also found that A. fumigatus extracts activated the TNF-α - converting enzyme (TACE), critical for the cleavage of membrane-bound pro - TGF-α, and its inhibition with lowmolecular 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-α/epidermal growth factor receptor pathway, may be a pathogenetic mechanism of allergic bronchopulmonary mycosis.

本文言語English
ページ(範囲)999-1005
ページ数7
ジャーナルJournal of Immunology
187
2
DOI
出版ステータスPublished - 2011 7 15

ASJC Scopus subject areas

  • 免疫アレルギー学
  • 免疫学

フィンガープリント

「Induction of Mucin and MUC5AC expression by the protease activity of aspergillus fumigatus in airway epithelial cells」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル