Origin and Consequences of Necroinflammation

Publikation: Beitrag in FachzeitschriftÜbersichtsartikel (Review)BeigetragenBegutachtung

Beitragende

Abstract

When cells undergo necrotic cell death in either physiological or pathophysiological settings in vivo, they release highly immunogenic intracellular molecules and organelles into the interstitium and thereby represent the strongest known trigger of the immune system. With our increasing understanding of necrosis as a regulated and genetically determined process (RN, regulated necrosis), necrosis and necroinflammation can be pharmacologically prevented. This review discusses our current knowledge about signaling pathways of necrotic cell death as the origin of necroinflammation. Multiple pathways of RN such as necroptosis, ferroptosis, and pyroptosis have been evolutionary conserved most likely because of their differences in immunogenicity. As the consequence of necrosis, however, all necrotic cells release damage associated molecular patterns (DAMPs) that have been extensively investigated over the last two decades. Analysis of necroinflammation allows characterizing specific signatures for each particular pathway of cell death. While all RN-pathways share the release of DAMPs in general, most of them actively regulate the immune system by the additional expression and/or maturation of either pro- or anti-inflammatory cytokines/chemokines. In addition, DAMPs have been demonstrated to modulate the process of regeneration. For the purpose of better understanding of necroinflammation, we introduce a novel classification of DAMPs in this review to help detect the relative contribution of each RN-pathway to certain physiological and pathophysiological conditions.

Details

OriginalspracheEnglisch
Seiten (von - bis)727-780
Seitenumfang54
FachzeitschriftPhysiological reviews
Jahrgang98
Ausgabenummer2
PublikationsstatusVeröffentlicht - 1 Apr. 2018
Peer-Review-StatusJa

Externe IDs

Scopus 85042797616
ORCID /0000-0001-6287-9725/work/145698898
ORCID /0000-0002-9728-1413/work/145699164

Schlagworte

Schlagwörter

  • Animals, Apoptosis/physiology, Cell Death/physiology, Cytokines/immunology, Humans, Inflammation/immunology, Necrosis/metabolism, Signal Transduction/physiology