Regulated cell death and inflammation: an auto-amplification loop causes organ failure
Regulated cell death and inflammation: an auto-amplification loop causes organ failure
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DOI：
10.1038/nri3743
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发表时间：
2014-11-01
影响因子：
100.3
通讯作者：
Anders, Hans-Joachim
中科院分区：
文献类型：
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作者：
Linkermann, Andreas;Stockwell, Brent R.;Anders, Hans-Joachim
调节性细胞死亡（RCD）是免疫沉默或免疫原性。实质细胞中的RCD可能导致释放损伤相关的分子模式，这些分子模式驱动组织炎症和RCD进一步途径的激活。在调节性坏死的初始事件之后，RCD和炎症可以相互诱导并驱动局部自动放大环，导致过度的细胞死亡和炎症。在这篇观点文章中，我们提出促炎和RCD通路之间的这种串扰在实体器官衰竭、移植和癌症中具有病理生理学相关性。在我们看来，临床医生不仅应该处方免疫抑制治疗来破坏这一回路，而且还应该实施被忽视的治疗选择，即添加干扰RCD的化合物。
Regulated cell death (RCD) is either immunologically silent or immunogenic. RCD in parenchymal cells may lead to the release of damage-associated molecular patterns that drive both tissue inflammation and the activation of further pathways of RCD. Following an initial event of regulated necrosis, RCD and inflammation can induce each other and drive a local auto-amplification loop that leads to exaggerated cell death and inflammation. In this Opinion article, we propose that such crosstalk between pro-inflammatory and RCD pathways has pathophysiological relevance in solid organ failure, transplantation and cancer. In our opinion, clinicians should not only prescribe immunosuppressive treatments to disrupt this circuit, but also implement the neglected therapeutic option of adding compounds that interfere with RCD.