ZFIN ID: ZDB-PUB-131204-9
Zebrafish tissue injury causes up-regulation of interleukin-1 and caspase dependent amplification of the inflammatory response
Ogryzko, N.V., Hoggett, E.E., Solaymani-Kohal, S., Tazzyman, S., Chico, T.J., Renshaw, S.A., and Wilson, H.L.
Date: 2014
Source: Disease models & mechanisms   7(2): 259-64 (Journal)
Registered Authors: Chico, Tim J., Ogryzko, Nikolay, Renshaw, Steve A.
Keywords: none
MeSH Terms:
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/analogs & derivatives
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/pharmacology
  • Animal Fins/drug effects
  • Animal Fins/pathology
  • Animals
  • Caspase 1/metabolism*
  • Caspase Inhibitors/pharmacology
  • Conserved Sequence
  • Down-Regulation/drug effects
  • Embryo, Nonmammalian/drug effects
  • Embryo, Nonmammalian/metabolism
  • Embryo, Nonmammalian/pathology
  • Humans
  • Inflammation/pathology*
  • Interleukin-1beta/metabolism*
  • Leukocytes/drug effects
  • Leukocytes/metabolism
  • NF-kappa B/metabolism
  • Rosaniline Dyes/pharmacology
  • Signal Transduction/drug effects
  • Up-Regulation*/drug effects
  • Zebrafish/embryology
  • Zebrafish/metabolism*
PubMed: 24203886 Full text @ Dis. Model. Mech.

Interleukin-1, the 'gate-keeper' 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 is tightly controlled, whilst 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 where 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-1β shares a beta-sheet rich trefoil structure with its human counterpart. Functionally, leukocyte expression of IL-1β was detectable only following injury, which activated leukocytes throughout zebrafish embryos. Migration of macrophages and neutrophils was attenuated by caspase-1 and P2X7 inhibitors, which similarly inhibited the activation of NF-κB at the site of injury. Zebrafish offer a new and versatile model to study the IL-1β pathway in inflammatory disease and should offer unique insights into IL-1 biology in vivo.