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dc.contributor.authorCreagh, Emmaen
dc.contributor.authorO'Sullivan, Jacinthaen
dc.contributor.authorReynolds, Johnen
dc.contributor.authorRavi, Narayanasamyen
dc.date.accessioned2020-10-19T12:23:16Z
dc.date.available2020-10-19T12:23:16Z
dc.date.issued2020en
dc.date.submitted2020en
dc.identifier.citationG. Barber, A. Anand, K. Oficjalska, J.J. Phelan, A. B. Heeran, E. Flis, N. E. Clarke, J. A. Watson, J. Strangmann, B. Flood, H. O Neill, D. O Toole, F. MacCarthy, N. Ravi, J. V. Reynolds, E.W. Kay, M. Quante, J. O Sullivan, E.M. Creagh., Characterizing caspase-1 involvement during esophageal disease progression., Cancer Immunology Immunotherapy, 69, 12, 2020, 2635 - 2649en
dc.identifier.issn0340-7004en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/93838
dc.descriptionPUBLISHEDen
dc.description.abstractBarrett’s esophagus (BE) is an inflammatory condition and a neoplastic precursor to esophageal adenocarcinoma (EAC). Inflammasome signaling, which contributes to acute and chronic inflammation, results in caspase-1 activation leading to the secretion of IL-1β and IL-18, and inflammatory cell death (pyroptosis). This study aimed to characterize caspase-1 expression, and its functional importance, during disease progression to BE and EAC. Three models of disease progression (Normal–BE–EAC) were employed to profile caspase-1 expression: (1) a human esophageal cell line model; (2) a murine model of BE; and (3) resected tissue from BE-associated EAC patients. BE patient biopsies and murine BE organoids were cultured ex vivo in the presence of a caspase-1 inhibitor, to determine the importance of caspase-1 for inflammatory cytokine and chemokine secretion. Epithelial caspase-1 expression levels were significantly enhanced in BE (p < 0.01). In contrast, stromal caspase-1 levels correlated with histological inflammation scores during disease progression (p < 0.05). Elevated secretion of IL-1β from BE explanted tissue, compared to adjacent normal tissue (p < 0.01), confirmed enhanced activity of caspase-1 in BE tissue. Caspase-1 inhibition in LPS-stimulated murine BE organoids caused a significant reduction in IL-1β (p < 0.01) and CXCL1 (p < 0.05) secretion, confirming the importance of caspase-1 in the production of cytokines and chemokines associated with disease progression from BE to EAC. Targeting caspase-1 activity in BE patients should therefore be tested as a novel strategy to prevent inflammatory complications associated with disease progression.en
dc.format.extent2635en
dc.format.extent2649en
dc.language.isoenen
dc.relation.ispartofseriesCancer Immunology Immunotherapyen
dc.relation.ispartofseries69en
dc.relation.ispartofseries12en
dc.rightsYen
dc.subjectEsophageal canceren
dc.subjectInflammationen
dc.subjectBarrett’s metaplasiaen
dc.subjectInflammasomeen
dc.titleCharacterizing caspase-1 involvement during esophageal disease progression.en
dc.typeJournal Articleen
dc.contributor.sponsorEuropean Union (EU)en
dc.contributor.sponsorTCDen
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/ecreaghen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/osullij4en
dc.identifier.peoplefinderurlhttp://people.tcd.ie/ravinen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/reynoljven
dc.identifier.rssinternalid217058en
dc.identifier.doi10.1007/s00262-020-02650-4en
dc.rights.ecaccessrightsopenAccess
dc.contributor.sponsorGrantNumber721906en
dc.subject.TCDThemeCanceren
dc.subject.TCDThemeImmunology, Inflammation & Infectionen
dc.subject.TCDTagBARRETTS ESOPHAGUSen
dc.subject.TCDTagInflammasome-mediated inflammationen
dc.subject.TCDTagOesophageal Canceren
dc.subject.TCDTagcaspase-1en
dc.identifier.orcid_id0000-0001-7631-4370en
dc.subject.darat_impairmentChronic Health Conditionen
dc.subject.darat_thematicHealthen
dc.status.accessibleNen


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