Vanden Berghe Tom, Kaiser William J, Bertrand Mathieu Jm, Vandenabeele Peter
Inflammation Research Center; VIB; Ghent, Belgium; Department of Biomedical Molecular Biological; Ghent University; Ghent, Belgium.
Department of Microbiology and Immunology; Emory Vaccine Center; Emory University School of Medicine ; Atlanta, GA, USA.
Mol Cell Oncol. 2015 Apr 8;2(4):e975093. doi: 10.4161/23723556.2014.975093. eCollection 2015 Oct-Dec.
Our current knowledge of the molecular mechanisms regulating the signaling pathways leading to cell survival, cell death, and inflammation has shed light on the tight mutual interplays between these processes. Moreover, the fact that both apoptosis and necrosis can be molecularly controlled has greatly increased our interest in the roles that these types of cell death play in the control of general processes such as development, homeostasis, and inflammation. In this review, we provide a brief update on the different cell death modalities and describe in more detail the intracellular crosstalk between survival, apoptotic, necroptotic, and inflammatory pathways that are activated downstream of death receptors. An important concept is that the different cell death processes modulate each other by mutual inhibitory mechanisms, serve as alternative back-up death routes in the case of a defect in the first-line cell death response, and are controlled by multiple feedback loops. We conclude by discussing future perspectives and challenges in the field of cell death and inflammation research.
我们目前对调节导致细胞存活、细胞死亡和炎症的信号通路的分子机制的了解，揭示了这些过程之间紧密的相互作用。此外，凋亡和坏死都可以受到分子控制这一事实，极大地增加了我们对这些类型的细胞死亡在发育、体内平衡和炎症等一般过程控制中所起作用的兴趣。在这篇综述中，我们简要介绍了不同的细胞死亡方式，并更详细地描述了在死亡受体下游激活的存活、凋亡、坏死性凋亡和炎症信号通路之间的细胞内串扰。一个重要的概念是，不同的细胞死亡过程通过相互抑制机制相互调节，在一线细胞死亡反应存在缺陷的情况下作为替代的备用死亡途径，并由多个反馈回路控制。我们通过讨论细胞死亡和炎症研究领域的未来前景和挑战来结束本文。
