Fas ligand released by activated monocytes causes apoptosis of lung epithelial cells in human acute lung injury model in vitro.
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.
Mizuta
Mitsuhiko
M
Department of Anesthesiology and Intensive Care, Kyoto Prefectural University of Medicine, 465 Kajiicho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
Nakajima
Hiroo
H
Mizuta
Naruhiko
N
Kitamura
Yoshihiro
Y
Nakajima
Yasufumi
Y
Hashimoto
Soshi
S
Matsuyama
Hiroki
H
Shime
Nobuaki
N
Amaya
Fumimasa
F
Koh
Hidefumi
H
Ishizaka
Akitoshi
A
Magae
Junji
J
Tanuma
Sei-ich
SI
Hashimoto
Satoru
S
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
D017077:Culture Media, Conditioned; C491901:FAS protein, human; D053222:Fas Ligand Protein; D008070:Lipopolysaccharides; D034741:RNA, Small Interfering; D019014:fas Receptor