‘Necrosome’-induced inflammation: must cells die for it?

Necrosis, a form of death characterized by rupture of the cell membrane, is closely interlinked with inflammation. Cellular components released during necrotic death can trigger inflammation. Conversely, inflammation often yields tissue damage and, as a consequence, cell death. Which occurs first – necrosis or inflammation – in specific in vivo situations is currently difficult to tell. A way out of this ‘chicken-and-egg’ conundrum may be found via the recent finding that both necrotic cell death and inflammation can be initiated by a distinct set of signaling proteins, the ‘necrosome’, that includes receptor-interacting protein (RIP)1, RIP3 and caspase-8. Further clarifying the function of these signaling proteins should make it possible to establish when they induce inflammation directly and when inflammation is caused by necrotic cell death.