However, although it was reported that processing of IL-1β by a gilthead sea bream fibroblast cell line is abrogated by a specific caspase-1 inhibitor, neither direct evidence for the participation of caspase-1 in this processing event was provided nor the cleavage site in pro IL-1β was defined. IL-1β has been identified in several fish species, ,, ,, ,, ,. Non-caspase-1-mediated cleavage mechanisms generating different active forms of IL-1β have also been described (reviewed in, ,, ). In humans and mice, caspase-1, also known as ICE (interleukin-1β converting enzyme), ,, specifically cleaves proIL-1β after aspartate 116 and 117, respectively, yielding a C-terminal 17.5 kDa secreted active form, ,, ,. In mammals, IL-1β is synthesized as an inactive 31 kDa signal peptide-less precursor molecule (proIL-1β). These signaling pathways activate in turn the transcription factors NF-κB and AP-1, resulting in the induction of genes encoding chemokines, cytokines, acute-phase proteins, cell adhesion molecules, and enzymes involved in the production of small pro-inflammatory substances.
IL-1β exerts its activity by binding to IL-1 type I receptor (IL-1RI), which then recruits IL-1 receptor accessory protein (IL-1RAP) forming a complex that triggers a series of phosphorylation events leading to the activation of IκB kinase (IKK) and MAPK pathways (see e.g.,, , ). It is mainly produced by activated macrophages, monocytes, and dendritic cells and affects almost every cell type, playing a central role in the generation of systemic and local responses to infection, injury, and immunological challenges, although it can also have detrimental effects (see e.g.,, ,, ,, ). IL-1β is the most studied pro-inflammatory cytokine, much due to its role in mediating auto-inflammatory diseases (see e.g.,, ,, ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: The authors have declared that no competing interests exist.
AdV was supported by Programa Ciência – financed by Programa Operacional Potencial Humano POPH – QREN – Tipologia 4.2 – Promoção do Emprego Científico, co-funded by Fundo Social Europeu and National funding from Ministry of Science, Technology and Higher Education (MCTES). MIRR was the recipient of FCT fellowship SFRH/BD/37717/2007. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.įunding: This work was supported by a grant (PTDC/CVT/69086/2006 FCOMP-01-0124-FEDER-007173) from the Portuguese Science and Technology Foundation (FCT).
Received: JAccepted: OctoPublished: November 30, 2012Ĭopyright: © 2012 Reis et al. Finally, it is shown that sea bass and avian IL-1β are specifically cleaved by caspase-1 at different but phylogenetically conserved aspartates, distinct from the cleavage site of mammalian IL-1β.Ĭitation: Reis MIR, do Vale A, Pereira PJB, Azevedo JE, dos Santos NMS (2012) Caspase-1 and IL-1β Processing in a Teleost Fish. The existence of caspase-1 isoforms in fish and in mammals suggests that they have been evolutionarily maintained and therefore are likely to play a regulatory role in the inflammatory response, as shown for other caspases. Moreover, the presence of alternatively spliced variants of caspase-1 in sea bass is reported.
In this work it is shown that sea bass caspase-1 auto-processing is similar to that of the human enzyme, resulting in active p24/p10 and p20/p10 heterodimers. Recently, fish caspase-1 orthologues have been identified in sea bass ( Dicentrarchus labrax) and sea bream ( Sparus aurata) but very little is known regarding their processing and activity. The caspase-1 cleavage site strictly conserved in all mammalian IL-1β sequences is absent in IL-1β sequences reported for non-mammalian vertebrates. In mammals, IL-1β is synthesized as an inactive 31 kDa precursor that is cleaved by caspase-1 generating a 17.5 kDa secreted active mature form. Interleukine-1β (IL-1β) is the most studied pro-inflammatory cytokine, playing a central role in the generation of systemic and local responses to infection, injury, and immunological challenges.