Fas Ligand Released by Activated Monocytes Causes Apoptosis of Lung Epithelial Cells in Human Acute Lung Injury Model in Vitro

• Published in: Biological & Pharmaceutical Bulletin Vol. 31; no. 3; pp. 386 - 390
• Main Authors: Mizuta, Mitsuhiko, Nakajima, Hiroo, Mizuta, Naruhiko, Kitamura, Yoshihiro, Nakajima, Yasufumi, Hashimoto, Soshi, Matsuyama, Hiroki, Shime, Nobuaki, Amaya, Fumimasa, Koh, Hidefumi, Ishizaka, Akitoshi, Magae, Junji, Tanuma, Sei-ich, Hashimoto, Satoru
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 01.03.2008; Pharmaceutical Society of Japan; Japan Science and Technology Agency
• Subjects: Acute Disease; acute lung injury; acute respiratory distress syndrome; apoptosis; Apoptosis - drug effects; Apoptosis - genetics; Cell Line, Tumor; Culture Media, Conditioned; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Epithelial Cells - pathology; Fas; Fas ligand; Fas Ligand Protein - genetics; Fas Ligand Protein - metabolism; Fas Ligand Protein - physiology; fas Receptor - biosynthesis; fas Receptor - genetics; Humans; Lipopolysaccharides - pharmacology; Lung - cytology; Lung - drug effects; Lung - pathology; Lung Diseases - etiology; Lung Diseases - metabolism; Lung Diseases - pathology; Monocytes - cytology; Monocytes - drug effects; Monocytes - metabolism; RNA Interference; RNA, Small Interfering - genetics; Transfection
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.31.386

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.