title: Fas/CD95-induced chemokines can serve as "find-me" signals for apoptotic cells.
abstract: Apoptosis is commonly thought to represent an immunologically silent or even anti-inflammatory mode of cell death, resulting in cell clearance in the absence of explicit activation of the immune system. However, here we show that Fas/CD95-induced apoptosis is associated with the production of an array of cytokines and chemokines, including IL-6, IL-8, CXCL1, MCP-1, and GMCSF. Fas-induced production of MCP-1 and IL-8 promoted chemotaxis of phagocytes toward apoptotic cells, suggesting that these factors serve as "find-me" signals in this context. We also show that RIPK1 and IAPs are required for optimal production of cytokines and chemokines in response to Fas receptor stimulation. Consequently, a synthetic IAP antagonist potently suppressed Fas-dependent expression of multiple proinflammatory mediators and inhibited Fas-induced chemotaxis. Thus, in addition to provoking apoptosis, Fas receptor stimulation can trigger the secretion of chemotactic factors and other immunologically active proteins that can influence immune responsiveness toward dying cells.
authors: Molecular Cell Biology Laboratory, Department of Genetics, The Smurfit Institute, Trinity College, Dublin 2, Ireland.
authors: Sean P
authors: SP
authors: Cullen
authors: Conor M
authors: CM
authors: Henry
authors: Conor J
authors: CJ
authors: Kearney
authors: Susan E
authors: SE
authors: Logue
authors: Maria
authors: M
authors: Feoktistova
authors: Graham A
authors: GA
authors: Tynan
authors: Ed C
authors: EC
authors: Lavelle
authors: Martin
authors: M
authors: Leverkus
authors: Seamus J
authors: SJ
authors: Martin
mesh_terms: D000818:Animals; D017209:Apoptosis; D053181:Caspase 8 / Q000378:metabolism; D018932:Chemokine CCL2 / Q000378:metabolism / Q000502:physiology*; D018925:Chemokines / Q000378:metabolism / Q000502:physiology; D002633:Chemotaxis; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D010586:Phagocytes / Q000502:physiology; D011485:Protein Binding; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction; D019014:fas Receptor / Q000378:metabolism / Q000502:physiology*
chemical_list: C111835:CCL2 protein, human; C508606:CXCL8 protein, human; D018932:Chemokine CCL2; D018925:Chemokines; C491901:FAS protein, human; D018836:Inflammation Mediators; D051034:Inhibitor of Apoptosis Proteins; D016209:Interleukin-8; D016328:NF-kappa B; D019014:fas Receptor; C506249:RIPK1 protein, human; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; C505530:CASP8 protein, human; D053181:Caspase 8