title: Silica and double-stranded RNA synergistically induce bronchial epithelial apoptosis and airway inflammation.
abstract: Silica crystals (silica), which are the main mineral component of volcanic ash and desert dust, can activate the caspase-1-activating inflammasome in phagocytic cells to secrete IL-1β. Although inhalation of silica-containing dust is known to exacerbate chronic respiratory diseases, probably through inflammasome activation, its direct effects on bronchial epithelial cells remain unclear. Here, we show that silica and double-stranded RNA (dsRNA) synergistically induces caspase-9-dependent apoptosis, but not inflammasome activation, of bronchial epithelial cells. Intranasal administration of silica and dsRNA to mice synergistically enhanced neutrophil infiltration in the airway without IL-1β release in the bronchoalveolar lavage fluid. Histopathological analysis revealed that silica or dsRNA alone induced slight airway inflammation, whereas combined administration significantly enhanced airway inflammation and epithelial damage. These novel findings suggest that inhalation of silica-containing dust may cause inflammasome-independent airway inflammation, possibly by damaging the epithelial barrier, especially at the time of viral infection. These responses may also be involved in acute lung injury caused by inhaled silica-containing dust.
authors.affiliation: 1 Department of Pediatrics, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Unno
authors.forename: Kyoko
authors.initials: K
authors.lastname: Futamura
authors.forename: Hideaki
authors.initials: H
authors.lastname: Morita
authors.forename: Reiji
authors.initials: R
authors.lastname: Kojima
authors.forename: Ken
authors.initials: K
authors.lastname: Arae
authors.forename: Susumu
authors.initials: S
authors.lastname: Nakae
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ida
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Saito
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Akio
authors.initials: A
authors.lastname: Matsuda
mesh_terms: D000281:Administration, Intranasal; D000393:Air Pollutants / Q000737:chemistry; D000818:Animals; D017209:Apoptosis; D001980:Bronchi / Q000166:cytology / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid; D053453:Caspase 9 / Q000378:metabolism*; D002470:Cell Survival; D004391:Dust; D004847:Epithelial Cells / Q000166:cytology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D053583:Interleukin-1beta / Q000378:metabolism; D008168:Lung / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D011070:Poly I-C / Q000737:chemistry; D012330:RNA, Double-Stranded / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000378:metabolism; D012822:Silicon Dioxide / Q000737:chemistry*
chemical_list: D000393:Air Pollutants; D004391:Dust; D053583:Interleukin-1beta; D012330:RNA, Double-Stranded; D012822:Silicon Dioxide; C506433:CASP9 protein, human; C506434:Casp9 protein, mouse; D053453:Caspase 9; D011070:Poly I-C
keywords: apoptosis; bronchial epithelial cells; caspase; double-stranded RNA; silica crystals