title: Necroptosis: the release of damage-associated molecular patterns and its physiological relevance.
abstract: Regulated necrosis, termed necroptosis, is negatively regulated by caspase-8 and is dependent on the kinase activity of RIPK1 and RIPK3. Necroptosis leads to rapid plasma membrane permeabilization and to the release of cell contents and exposure of damage-associated molecular patterns (DAMPs). We are only beginning to identify the necroptotic DAMPs, their modifications, and their potential role in the regulation of inflammation. In this review, we discuss the physiological relevance of necroptosis and its role in the modulation of inflammation. For example, during viral infection, RIPK3-mediated necroptosis acts as a backup mechanism to clear pathogens. Necroptosis is also involved in apparently immunologically silent maintenance of T cell homeostasis. In contrast, the induction of necroptosis in skin, intestine, systemic inflammatory response syndrome, and ischemia reperfusion injury provoke a strong inflammatory response, which might be triggered by emission of DAMPs from necroptotic cells, showing the detrimental side of necroptosis.
authors: Molecular Signaling and Cell Death Unit, Department for Molecular Biomedical Research, VIB, 9052 Ghent, Belgium.
authors: Agnieszka
authors: A
authors: Kaczmarek
authors: Peter
authors: P
authors: Vandenabeele
authors: Dmitri V
authors: DV
authors: Krysko
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D001419:Bacteria / Q000254:growth & development; D001424:Bacterial Infections / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D053181:Caspase 8 / Q000235:genetics / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D009336:Necrosis / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000235:genetics / Q000276:immunology; D051192:Receptors, Pattern Recognition / Q000235:genetics / Q000276:immunology; D015427:Reperfusion Injury / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014777:Virus Diseases / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D014780:Viruses / Q000254:growth & development
chemical_list: D051192:Receptors, Pattern Recognition; C506249:RIPK1 protein, human; C119705:RIPK3 protein, human; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; D053181:Caspase 8