Anti-inflammatory functions of the "apoptotic" caspases
Anti-inflammatory functions of the "apoptotic" caspases
复制标题
DOI：
10.1111/j.1749-6632.2010.05742.x
复制
发表时间：
2010-01-01
期刊：
影响因子：
--
通讯作者：
Kovalenko, Andrew
中科院分区：
文献类型：
--
作者：
Wallach, David;Kang, Tae-Bong;Kovalenko, Andrew
半胱天冬酶的两个主要已知功能在调节炎症方面发挥拮抗作用。 “炎性”半胱天冬酶通过催化 IL-1 β 前体和其他促炎细胞因子的加工来引发炎症。相比之下，“凋亡”半胱天冬酶通过施加细胞死亡形式来防止炎症的触发，这种细胞死亡形式阻止垂死细胞释放警报素并指示抗炎介质的产生。这些拮抗功能是由进化相关机制发挥的。 caspase-8 是一种响应 TNF 家族配体而介导细胞凋亡诱导的酶，对其功能的研究表明，它还能以其他方式阻断炎症。一种方法是通过外源核糖核酸限制 RIG-I 复合物的活化。表皮 caspase-8 缺陷的小鼠的慢性皮肤炎症与角质形成细胞中 RIG-I 复合物的组成性激活有关。这种激活显然是由表皮细胞释放的核酸引起的，这些核酸在角质化过程中分解，并且由于不受 caspase-8 的限制而变得慢性。
The two main known functions of the caspases act antagonistically in regulating inflammation. "Inflammatory" caspases trigger inflammation by catalyzing the processing of IL-1 beta precursors and other proinflammatory cytokines. In contrast, "apoptotic" caspases safeguard against the triggering of inflammation by imposing a cell-death form that withholds release of alarmins by dying cells and dictates generation of anti-inflammatory mediators. These antagonizing functions are exerted by evolution-related mechanisms. Studies of the function of caspase-8, an enzyme-mediating apoptotic cell-death induction in response to TNF-family ligands, reveal that it blocks inflammation in additional ways. One way is by restricting activation of the RIG-I complex by foreign ribonucleic acid. Chronic skin inflammation in mice with caspase-8 deficient epidermis is associated with constitutive activation of the RIG-I complex in keratinocytes. This activation is apparently prompted by nucleic acids released from epidermal cells that disintegrate during cornification, and becomes chronic because it is not restricted by caspase-8.