Identification and functional characterization of a new IL-1 family member, IL-1Fm2, in most evolutionarily advanced fish
Angosto, D., Montero, J., López-Muñoz, A., Alcaraz-Pérez, F. Bird, S., …, Mulero, V. (203). Identification and functional characterization of a new IL-1 family member, IL-1Fm2, in most evolutionarily advanced fish. Innate Immunity, published online on 12 September, 2013.
Permanent Research Commons link: https://hdl.handle.net/10289/7997
The IL-1 family consists of 11 members that play an important role as key mediators in inflammation and immunity. Here, we report the identification of a new member of the IL-1 family (IL-1Fm2) that is present in species belonging to the most evolutionarily advanced group of teleost fish (Series Percomorpha), including Perciformes, Beloniformes, Gasterosteiformes, Cyprinodontiformes and Pleuronectiformes. However, IL-1Fm2 seems to be absent in Tetraodontiformes, which also belong to the Percomorpha. The expression pattern of gilthead seabream IL-1Fm2 revealed that although it was hardly induced by PAMPs, the combination of PAMPs and recombinant IL-1Fm2 synergistically induced its expression in macrophages and granulocytes. In addition, recombinant IL-1Fm2 was able to activate the respiratory burst of seabream phagocytes and to synergistically induce the expression of IL-1β, TNF-α, IL-8 and IL-10 when combined with PAMPs. Finally, although gilthead seabream IL-1Fm2 did not show a conserved caspase-1 processing site, macrophages processed IL-1Fm2 before being released. However, both pan-caspase and caspase-1 inhibitors failed to inhibit the processing and release of IL-1Fm2. These results demonstrate an important role of IL-1Fm2 in the regulation of fish immune responses, shed light on the evolution of the IL-1 family in vertebrates and point to the complexity of this cytokine family.