Zebrafish tissue injury causes up-regulation of interleukin-1 and caspase dependent amplification of the inflammatory response
- Authors
- Ogryzko, N.V., Hoggett, E.E., Solaymani-Kohal, S., Tazzyman, S., Chico, T.J., Renshaw, S.A., and Wilson, H.L.
- ID
- ZDB-PUB-131204-9
- 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.