title: Seawater induces apoptosis in alveolar epithelial cells via the Fas/FasL-mediated pathway.
abstract: Our previous study showed that seawater can cause lung tissue cell apoptosis; in the present study, the immunohistochemistry and Western blot analysis results demonstrated that Fas, FasL, and cleaved caspase-8 and caspase-3 were up-regulated in the rat lungs exposed to seawater. We found that seawater-induced human lung alveolar epithelial A549 cell apoptosis was concentration and time dependent. Moreover, seawater increased the expression of Fas, FasL, and cleaved caspase-8 and caspase-3 in A549 cells. The incubation of A549 cells in the presence of FasL-neutralising antibody (NOK-2) or caspase-8 inhibitor (Z-IETD-FMK) resulted in a decrease of seawater-induced cell apoptosis. NOK-2 inhibited Fas/FasL interaction and reduced the cleavage of caspase-8 and caspase-3, and Z-IETD-FMK blocked caspase-8 and caspase-3 activation. Seawater similarly produced a significant increase in rat alveolar type II cell apoptosis and expression of Fas and cleaved caspase-8. In summary, the Fas/FasL pathway involved in alveolar epithelial cell (AEC) apoptosis could be important in the pathogenesis of seawater-induced acute lung injury (SW-ALI).
authors.affiliation: Department of Respiratory Medicine, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, PR China.
authors.forename: Feng
authors.initials: F
authors.lastname: Han
authors.forename: Ying
authors.initials: Y
authors.lastname: Luo
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Li
authors.forename: Zhongyang
authors.initials: Z
authors.lastname: Liu
authors.forename: Dunquan
authors.initials: D
authors.lastname: Xu
authors.forename: Faguang
authors.initials: F
authors.lastname: Jin
authors.forename: Zhichao
authors.initials: Z
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D004332:Drowning / Q000378:metabolism / Q000503:physiopathology; D004847:Epithelial Cells / Q000378:metabolism*; D053222:Fas Ligand Protein / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D011650:Pulmonary Alveoli / Q000378:metabolism*; D051381:Rats; D012623:Seawater / Q000009:adverse effects*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D019014:fas Receptor / Q000378:metabolism*
chemical_list: D053222:Fas Ligand Protein; D019014:fas Receptor; D053148:Caspase 3; D053181:Caspase 8