Role of caspase-8 in hepatocyte response to infection and injury in mice
Role of caspase-8 in hepatocyte response to infection and injury in mice
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DOI：
10.1002/hep.21495
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发表时间：
2007-04-01
期刊：
影响因子：
13.5
通讯作者：
Wallach, David
中科院分区：
文献类型：
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作者：
Ben Moshe, Tehila;Barash, Hila;Wallach, David
半胱天冬酶-8与凋亡性细胞死亡和某些非凋亡功能的信号传导有关。然而，这种酶的实际生理或病理生理过程的知识是缺乏的。使用小鼠模型并采用条件性敲除方法来特异性地删除肝脏中的caspase-8基因，我们发现肝细胞中的caspase-8缺陷促进单核细胞增生李斯特菌对肝脏的感染，在部分肝切除术后的前48小时内减弱肝细胞增殖波，并且根据小鼠的遗传背景，提示对肝切除术的慢性炎症反应，其结果是，肝细胞的增殖虽然最初受到抑制，但随后可能持续增强，导致显著的肝肿大。总结：这些发现表明，caspase-8参与调节细胞对感染和损伤的反应，并且通过影响各种细胞功能，包括细胞死亡，细胞增殖和炎症诱导来实现。
Caspase-8 has been implicated in signaling for apoptotic cell death and for certain nonapoptotic functions. However, knowledge of actual physiological or pathophysiological processes to which this enzyme contributes is lacking. Using a mouse model and employing the conditional knockout approach to delete the caspase-8 gene specifically in the liver, we found that caspase-8 deficiency in hepatocytes facilitates infection of the liver by Listeria monocytogenes, attenuates the hepatocyte proliferation wave during the first 48 hours after partial hepatectomy and, depending on the genetic background of the mice, prompts a chronic inflammatory response to the hepatectomy, as a result of which the proliferation of hepatocytcs, although initially suppressed, might later be persistently enhanced, resulting in significant hepatomegaly. Conclusion: These findings indicate that caspase-8 participates in regulation of the cellular response to infection and injury and that it does so by affecting various cellular functions, including cell death, cell proliferation, and induction of inflammation.