Faculty of Life Sciences, University of Manchester, Manchester, UK.
Cell Death Dis. 2012 Jul 5;3(7):e338. doi: 10.1038/cddis.2012.86.
Caspase-1, formerly known as interleukin (IL)-1-converting enzyme is best established as the protease responsible for the processing of the key pro-inflammatory cytokine IL-1β from an inactive precursor to an active, secreted molecule. Thus, caspase-1 is regarded as a key mediator of inflammatory processes, and has become synonymous with inflammation. In addition to the processing of IL-1β, caspase-1 also executes a rapid programme of cell death, termed pyroptosis, in macrophages in response to intracellular bacteria. Pyroptosis is also regarded as a host response to remove the niche of the bacteria and to hasten their demise. These processes are generally accepted as the main roles of caspase-1. However, there is also a wealth of literature supporting a direct role for caspase-1 in non-infectious cell death processes. This is true in mammals, but also in non-mammalian vertebrates where caspase-1-dependent processing of IL-1β is absent because of the lack of appropriate caspase-1 cleavage sites. This literature is most prevalent in the brain where caspase-1 may directly regulate neuronal cell death in response to diverse insults. We attempt here to summarise the evidence for caspase-1 as a cell death enzyme and propose that, in addition to the processing of IL-1β, caspase-1 has an important and a conserved role as a cell death protease.
半胱氨酸天冬氨酸蛋白酶-1（Caspase-1），又被称为白介素（IL）-1 转换酶，其作为一种蛋白酶，可将无活性的前体炎性细胞因子白细胞介素-1β（IL-1β）加工成有活性的分泌型分子，这一作用机制最为人们所熟知。因此，Caspase-1 被认为是炎症过程中的关键介质，也被称为炎症的同义词。除了加工 IL-1β，Caspase-1 还能在受到胞内细菌刺激时，迅速诱导巨噬细胞发生细胞死亡，即细胞焦亡。细胞焦亡也被认为是宿主清除细菌并加速其死亡的一种反应。这些过程通常被认为是 Caspase-1 的主要作用。然而，也有大量文献支持 Caspase-1 在非传染性细胞死亡过程中发挥直接作用。在哺乳动物中是如此，在缺乏适当 Caspase-1 切割位点的非哺乳动物脊椎动物中也是如此，因为 Caspase-1 依赖性的 IL-1β 加工缺失。在大脑中，这方面的文献最为丰富，其中 Caspase-1 可能直接调节神经元细胞死亡，以应对各种损伤。在这里，我们试图总结 Caspase-1 作为细胞死亡酶的证据，并提出除了加工 IL-1β 外，Caspase-1 作为细胞死亡蛋白酶具有重要且保守的作用。
