Last updated on: 23.11.2023

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Necroptosis (pyroptosis) is the term used to describe programmed inflammatory cell death (see also apoptosis). Although it has long been known that inflammatory immune responses are associated with the death of cells by necrosis (necroptosis), the mechanisms controlling this process are poorly understood. Many results suggest that in order to trigger necroptosis, immune cells must produce and receive signals from the important immune regulator interferon. Thus, IFN-β-induced necroptosis of macrophages occurs through IFN-stimulated "gene factor 3 (ISGF3) signaling," which leads to sustained expression of STAT1, STAT2, and IRF9 (see IRF9 gene below).

General information
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Myeloid cells play a crucial role in the maintenance of inflammation in various chronic diseases. The death of macrophages through programmed necrosis (necroptosis) plays an important role in inflammatory processes. Type I IFN signaling (IFN-I) plays an important role in the course of necroptosis. Macrophages lacking the IFN-α receptor type I (seeIFNAR1 gene below) are highly resistant to necroptosis after stimulation with LPS, polyinosinic-polycytidylic acid, TNF-α or IFN-β in the presence of caspase inhibitors.

IFN-I-induced pyroptosis (necroptosis) is triggered by both Toll/IL-1 receptor domain-dependent and independent mechanisms and results in persistent phosphorylation of the receptor-interacting protein 3-kinase(RIP3 protein kinase), leading to necroptosis.

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  1. Akira S et al (2006) Pathogen recognition and innate immunity. Cell 124: 783-801.
  2. He S et al (2011) Toll-like receptors activate programmed necrosis in macrophages through a receptor-interacting kinase-3-mediated pathway. Proc Natl Acad Sci 108: 20054-20059.
  3. Christofferson DE et al (2010) Necroptosis as an alternative form of programmed cell death. Curr Opin Cell Biol 22: 263-268.
  4. McComb S et al (2012) cIAP1 and cIAP2 limit macrophage necroptosis by inhibiting Rip1 and Rip3 activation. Cell Death Differ 19: 1791-1801.

Last updated on: 23.11.2023