title: Fas-induced death of a murine pulmonary epithelial cell line: modulation by inflammatory cytokines.
abstract: Here we report that a murine pulmonary epithelial cell line (LA-4) expresses Fas (CD95) under resting conditions. Exposure of untreated cells to an anti-Fas monoclonal antibody induces apoptosis in a time- and dose-dependent fashion as revealed by cell viability and by propidium iodide staining followed by FACS analysis. Fas surface expression was increased, in a time-dependent fashion, by the inflammatory cytokines IL-1beta and TNF-alpha. Other inflammatory mediators such as IFN-gamma or endothelin-1 were without any effect. This increase in Fas expression was associated with an increase in sensitivity to anti-Fas-induced apoptosis of LA-4 cells. IL-4, which is known to induce CD95 resistance in other cell types, did not protect LA-4 cells against anti-CD95-induced cell death. These results suggest that Fas-induced apoptosis of epithelial cells may contribute to the epithelial shedding observed in asthmatic airways.
authors.affiliation: Novartis Horsham Research Centre, UK.
authors.forename: A
authors.initials: A
authors.lastname: Trifilieff
authors.forename: Y
authors.initials: Y
authors.lastname: Futjitani
authors.forename: A J
authors.initials: AJ
authors.lastname: Coyle
authors.forename: C
authors.initials: C
authors.lastname: Bertrand
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D016923:Cell Death; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology*; D051379:Mice; D020545:Respiratory Mucosa / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D019014:fas Receptor / Q000276:immunology / Q000502:physiology*
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines; D019014:fas Receptor