Alternaria extract activates autophagy that induces IL-18 release from airway epithelial cells

Hiroki Murai, Shintaro Okazaki, Hisako Hayashi, Akiko Kawakita, Koa Hosoki, Motoko Yasutomi, Sanjiv Sur, Yusei Ohshima

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Alternaria alternata is a major outdoor allergen that causes allergic airway diseases. Alternaria extract (ALT-E) has been shown to induce airway epithelial cells to release IL-18 and thereby initiate Th2-type responses. We investigated the underlying mechanisms involved in IL-18 release from ALT-E-stimulated airway epithelial cells. Normal human bronchial epithelial cells and A549 human lung adenocarcinoma cells were stimulated with ALT-E in the presence of different inhibitors of autophagy or caspases. IL-18 levels in culture supernatants were measured by ELISA. The numbers of autophagosomes, an LC3-I to LC3-II conversion, and p62 degradation were determined by immunofluorescence staining and immunoblotting. 3-methyladenine and bafilomycin, which inhibit the formation of preautophagosomal structures and autolysosomes, respectively, suppressed ALT-E-induced IL-18 release by cells, whereas caspase 1 and 8 inhibitors did not. ALT-E-stimulation increased autophagosome formation, LC-3 conversion, and p62 degradation in airway epithelial cells. LPS-stimulation induced the LC3 conversion in A549 cells, but did not induce IL-18 release or p62 degradation. Unlike LPS, ALT-E induced airway epithelial cells to release IL-18 via an autophagy dependent, caspase 1 and 8 independent pathway. Although autophagy has been shown to negatively regulate canonical inflammasome activity in TLR-stimulated macrophages, our data indicates that this process is an unconventional mechanism of IL-18 secretion by airway epithelial cells.

Original languageEnglish (US)
Pages (from-to)969-974
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume464
Issue number4
DOIs
StatePublished - Mar 20 2015

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Keywords

  • Airway epithelial cells
  • Allergy
  • Alternaria
  • Asthma
  • Autophagy
  • Interleukin-18

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

Murai, H., Okazaki, S., Hayashi, H., Kawakita, A., Hosoki, K., Yasutomi, M., Sur, S., & Ohshima, Y. (2015). Alternaria extract activates autophagy that induces IL-18 release from airway epithelial cells. Biochemical and Biophysical Research Communications, 464(4), 969-974. https://doi.org/10.1016/j.bbrc.2015.05.076