title: Fas ligand released by activated monocytes causes apoptosis of lung epithelial cells in human acute lung injury model in vitro.
abstract: Alveolar epithelial cell death plays a crucial role in the progression of acute lung injury. We have demonstrated up-regulation of Fas expression on alveolar epithelial cells, and soluble Fas ligand secretion from inflammatory cells upon acute lung injury. Here we show that the lipopolysaccharide-stimulated human monocyte cell line THP-1 releases Fas ligand, and that conditioned medium from lipopolysaccharide-stimulated THP-1 cells induces apoptosis of the human pulmonary adenocarcinoma cell line A549. Activation of caspase-3 and -8 is associated with the apoptosis. Gene targeting on Fas in A549 cells by specific small interfering RNA impairs apoptosis induced by conditioned medium from activated THP-1, while that on Fas ligand in THP-1 cells impairs the apoptosis-inducing activity of the conditioned medium produced by lipopolysaccharide-stimulated cells. These results suggest that Fas ligand released by monocytes causes alveolar epithelial cell death through a Fas-dependent apoptotic mechanism in the development of acute lung injury.
authors.affiliation: Department of Anesthesiology and Intensive Care, Kyoto Prefectural University of Medicine, 465 Kajiicho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Mizuta
authors.forename: Hiroo
authors.initials: H
authors.lastname: Nakajima
authors.forename: Naruhiko
authors.initials: N
authors.lastname: Mizuta
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kitamura
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Nakajima
authors.forename: Soshi
authors.initials: S
authors.lastname: Hashimoto
authors.forename: Hiroki
authors.initials: H
authors.lastname: Matsuyama
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Shime
authors.forename: Fumimasa
authors.initials: F
authors.lastname: Amaya
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Koh
authors.forename: Akitoshi
authors.initials: A
authors.lastname: Ishizaka
authors.forename: Junji
authors.initials: J
authors.lastname: Magae
authors.forename: Sei-ich
authors.initials: SI
authors.lastname: Tanuma
authors.forename: Satoru
authors.initials: S
authors.lastname: Hashimoto
mesh_terms: D000208:Acute Disease; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000473:pathology*; D008171:Lung Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D014162:Transfection; D019014:fas Receptor / Q000096:biosynthesis / Q000235:genetics
chemical_list: D017077:Culture Media, Conditioned; C491901:FAS protein, human; D053222:Fas Ligand Protein; D008070:Lipopolysaccharides; D034741:RNA, Small Interfering; D019014:fas Receptor