title: The in vivo significance of necroptosis: lessons from exploration of caspase-8 function.
abstract: Emerging evidence indicates that necrotic cell death can be regulated by a specific set of signaling molecules. Studies showing that the same signaling molecules also trigger inflammation, and that when cells die necrotically some of the molecules they release facilitate inflammation, raised the possibility that the death induced by these signaling molecules ("necroptosis") serves to trigger inflammation. Here we briefly discuss the work done on the anti-inflammatory function of caspase-8 and its relation to the inhibitory effect of this enzyme on the induction of necroptosis. The studies imply that caspase-8 and the other proximal signaling proteins known to participate in the induction and regulation of necroptosis are too pleiotropic to serve as reliable molecular probes for determining the relative contribution of this death mode to in vivo processes.
authors.affiliation: Department of Biological Chemistry, The Weizmann Institute of Science, 76100 Rehovot, Israel. Electronic address: d.wallach@weizmann.ac.il.
authors.forename: David
authors.initials: D
authors.lastname: Wallach
authors.affiliation: Department of Biotechnology, College of Biomedical and Health Science, Konkuk University, Chung-Ju 380-701, Republic of Korea.
authors.forename: Tae-Bong
authors.initials: TB
authors.lastname: Kang
authors.affiliation: Department of Biological Chemistry, The Weizmann Institute of Science, 76100 Rehovot, Israel.
authors.forename: Seung-Hoon
authors.initials: SH
authors.lastname: Yang
authors.affiliation: Department of Biological Chemistry, The Weizmann Institute of Science, 76100 Rehovot, Israel.
authors.forename: Andrew
authors.initials: A
authors.lastname: Kovalenko
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000276:immunology; D017209:Apoptosis / Q000276:immunology*; D053181:Caspase 8 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D051379:Mice; D009336:Necrosis / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D053181:Caspase 8
keywords: Caspase-8; Inflammasome; Inflammation; Necroptosis; Necrosis