Evolution of inflammasome functions in vertebrates: Inflammasome and caspase-I trigger fish macrophage cell death but are dispensable for the processing of IL-IB
Members of the nucleotide binding and oligomerization domain-like receptors (NLRs) and the PYD and CARD domain containing adaptor protein (PYCARD) assemble into multi-protein platforms, termed inflammasomes, to mediate in the activation of caspase-1 and the subsequent secretion of IL-1β and IL-18, a...
| Autores: | , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2012 |
| País: | España |
| Institución: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/313845 |
| Acceso en línea: | http://hdl.handle.net/10261/313845 |
| Access Level: | acceso abierto |
| Palabra clave: | Centro Oceanográfico de Murcia Acuicultura |
| Sumario: | Members of the nucleotide binding and oligomerization domain-like receptors (NLRs) and the PYD and CARD domain containing adaptor protein (PYCARD) assemble into multi-protein platforms, termed inflammasomes, to mediate in the activation of caspase-1 and the subsequent secretion of IL-1β and IL-18, and the induction of pyroptotic cell death. While the recognition site for caspase-1 is well conserved in mammals, most of the non-mammalian IL-1β genes cloned so far lack this conserved site. We report here that stimulation or infection of seabream macrophages (MØ) led to the caspase-1-independent processing and release of IL-1β. In addition, several classical activators of the NLRP3 inflammasome failed to activate caspase-1 and to induce the processing and release of IL-1β. Furthermore, the processing of IL-1β in seabream MØ is not prevented by caspase-1 or pan-caspase inhibitors, and recombinant seabream caspase-1 failed to process IL-1β. However, the pharmacological inhibition of caspase-1 impaired Salmonella enterica sv. Typhimurium-induced cell death. These results suggest a role for the inflammasome and caspase-1 in the regulation of pyroptotic cell death in fish and support the idea that its use as a molecular platform for the processing of pro-inflammatory cytokines arose after the divergence of fish and tetrapods. |
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