title: Evolution of inflammasome functions in vertebrates: Inflammasome and caspase-1 trigger fish macrophage cell death but are dispensable for the processing of IL-1β.
abstract: 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.
authors.affiliation: Department of Cell Biology and Histology, Faculty of Biology, University of Murcia, Murcia, Spain.
authors.forename: Diego
authors.initials: D
authors.lastname: Angosto
authors.forename: Gloria
authors.initials: G
authors.lastname: López-Castejón
authors.forename: Azucena
authors.initials: A
authors.lastname: López-Muñoz
authors.forename: María P
authors.initials: MP
authors.lastname: Sepulcre
authors.forename: Marta
authors.initials: M
authors.lastname: Arizcun
authors.forename: José
authors.initials: J
authors.lastname: Meseguer
authors.forename: Victoriano
authors.initials: V
authors.lastname: Mulero
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D005075:Biological Evolution; D053468:CARD Signaling Adaptor Proteins; D020170:Caspase 1 / Q000276:immunology / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000276:immunology; D004269:DNA, Bacterial / Q000276:immunology; D005408:Flagellin / Q000276:immunology; D058847:Inflammasomes / Q000187:drug effects / Q000276:immunology*; D053583:Interleukin-1beta / Q000276:immunology / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D055503:Protein Multimerization; D011499:Protein Processing, Post-Translational / Q000187:drug effects / Q000276:immunology; D012481:Salmonella Infections, Animal / Q000276:immunology*; D012485:Salmonella typhi / Q000276:immunology*; D021541:Sea Bream / Q000276:immunology* / Q000382:microbiology
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D053468:CARD Signaling Adaptor Proteins; D003598:Cytoskeletal Proteins; D004269:DNA, Bacterial; D058847:Inflammasomes; D053583:Interleukin-1beta; C098738:N-acetyl-tyrosyl-valyl-alanyl-aspartyl chloromethyl ketone; C402202:PYCARD protein, human; D005408:Flagellin; D020170:Caspase 1