Pyroptosis

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).

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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