title: 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-1β shares a β-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 inhibitors of either caspase-1 or P2X7, 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.
authors.affiliation: Medical Research Council Centre for Developmental and Biomedical Genetics, University of Sheffield, Sheffield, S10 2TN, UK.
authors.forename: Nikolay V
authors.initials: NV
authors.lastname: Ogryzko
authors.forename: Emily E
authors.initials: EE
authors.lastname: Hoggett
authors.forename: Sara
authors.initials: S
authors.lastname: Solaymani-Kohal
authors.forename: Simon
authors.initials: S
authors.lastname: Tazzyman
authors.forename: Timothy J A
authors.initials: TJ
authors.lastname: Chico
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Renshaw
authors.forename: Heather L
authors.initials: HL
authors.lastname: Wilson
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D058500:Animal Fins / Q000187:drug effects / Q000473:pathology; D000818:Animals; D020170:Caspase 1 / Q000378:metabolism*; D061945:Caspase Inhibitors / Q000494:pharmacology; D017124:Conserved Sequence; D015536:Down-Regulation / Q000187:drug effects; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D053583:Interleukin-1beta / Q000378:metabolism*; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D012394:Rosaniline Dyes / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D015027:Zebrafish / Q000196:embryology / Q000378:metabolism*
chemical_list: D061945:Caspase Inhibitors; D053583:Interleukin-1beta; D016328:NF-kappa B; D012394:Rosaniline Dyes; C063302:KN 62; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D020170:Caspase 1; C004692:coomassie Brilliant Blue
keywords: Inflammation; Interleukin-1; Zebrafish