Zebrafish tissue injury causes upregulation of interleukin-1 and caspase-dependent amplification of the inflammatory response.

ABSTRACT: Interleukin-1 (IL-1), the 'gatekeeper' of inflammation, is the apical cytokine in a signalling cascade that drives the early response to injury or infection. Expression, processing and secretion of IL-1 are tightly controlled, and dysregulated IL-1 signalling has been implicated in a number of pathologies ranging from atherosclerosis to complications of infection. Our understanding of these processes comes from in vitro monocytic cell culture models as lines or primary isolates, in which a range and spectra of IL-1 secretion mechanisms have been described. We therefore investigated whether zebrafish embryos provide a suitable in vivo model for studying IL-1-mediated inflammation. Structurally, zebrafish IL-1? shares a ?-sheet-rich trefoil structure with its human counterpart. Functionally, leukocyte expression of IL-1? was detectable only following injury, which activated leukocytes throughout zebrafish embryos. Migration of macrophages and neutrophils was attenuated by inhibitors of either caspase-1 or P2X7, which similarly inhibited the activation of NF-?B at the site of injury. Zebrafish offer a new and versatile model to study the IL-1? pathway in inflammatory disease and should offer unique insights into IL-1 biology in vivo.

SUBMITTER: Ogryzko NV 

PROVIDER: S-EPMC3917246 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature