Fas ligand released by activated monocytes causes apoptosis of lung epithelial cells in human acute lung injury model in vitro
Fas ligand released by activated monocytes causes apoptosis of lung epithelial cells in human acute lung injury model in vitro
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DOI：
10.1248/bpb.31.386
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发表时间：
2008-03-01
影响因子：
2
通讯作者：
Hashimoto, Satoru
中科院分区：
文献类型：
--
作者：
Mizuta, Mitsuhiko;Nakajima, Hiroo;Hashimoto, Satoru
肺泡上皮细胞的死亡在急性肺损伤的发展过程中起着至关重要的作用。我们已经证实了急性肺损伤时肺泡上皮细胞Fas表达上调，炎性细胞分泌可溶性Fas配体。在这里，我们表明，脂多糖刺激的人单核细胞系THP-1释放Fas配体，从脂多糖刺激的THP-1细胞的条件培养基诱导人肺腺癌细胞系A549的凋亡。caspase-3和caspase-8的激活与细胞凋亡有关。特异性小干扰RNA（siRNA）靶向A549细胞中Fas基因可减弱活化THP-1条件培养液诱导细胞凋亡的作用，而靶向THP-1细胞中Fas配体基因可减弱脂多糖刺激细胞产生的条件培养液诱导细胞凋亡的作用。这些结果表明，在急性肺损伤的发展过程中，单核细胞释放的Fas配体通过Fas依赖的凋亡机制引起肺泡上皮细胞死亡。
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.