Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
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Fas Ligand Released by Activated Monocytes Causes Apoptosis of Lung Epithelial Cells in Human Acute Lung Injury Model in Vitro
Mitsuhiko MizutaHiroo NakajimaNaruhiko MizutaYoshihiro KitamuraYasufumi NakajimaSoshi HashimotoHiroki MatsuyamaNobuaki ShimeFumimasa AmayaHidefumi KohAkitoshi IshizakaJunji MagaeSei-ich TanumaSatoru Hashimoto
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2008 Volume 31 Issue 3 Pages 386-390

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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.

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© 2008 The Pharmaceutical Society of Japan
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