Flood, BrianManils Pacheco, JoanNulty, CiaraFlis, EwelinaKenealy, SineadBarber, GillianFay, JoannaH.G. Mills, KingstonKay, Elaine W.Creagh, Emma M.2023-02-062023-02-062019-04-040950-9232https://hdl.handle.net/2445/193139Murine inflammatory caspase-11 has an important role in intestinal epithelial inflammation and barrier function. Activation of the non-canonical inflammasome, mediated by caspase-11, serves as a regulatory pathway for the production of the proinflammatory cytokines IL-1β and IL-18, and has a key role in pyroptotic cell death. We have previously demonstrated a protective role for caspase-11 during dextran sulphate sodium (DSS)-induced colitis, however the importance of caspase-11 during colorectal tumour development remains unclear. Here, we show that Casp11−/− mice are highly susceptible to the azoxymethane (AOM)-DSS model of colitis-associated cancer (CAC), compared to their wild type (WT) littermates. We show that deficient IL-18 production occurs at initial inflammation stages of disease, and that IL-1β production is more significantly impaired in Casp11−/− colons during established CAC. We identify defective STAT1 activation in Casp11−/− colons during disease progression, and show that IL-1β signalling induces caspase-11 expression and STAT1 activation in primary murine macrophages and intestinal epithelial cells. These findings uncover an anti-tumour role for the caspase-11 and the non-canonical inflammasome during CAC, and suggest a critical role for caspase-11, linking IL-1β and STAT1 signalling pathways.17 p.application/pdfengcc by (c) Flood, Brian et al., 2019https://creativecommons.org/licenses/by/4.0/CarcinogènesiColitisInflamacióCàncer colorectalCarcinogenesisColitisInflammationColorectal cancerinfo:eu-repo/semantics/article7238462023-02-06info:eu-repo/semantics/openAccess30538296