Protective role for caspase-11 during acute experimental murine colitis.
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ABSTRACT:
SUBMITTER: Oficjalska K
PROVIDER: S-EPMC4298125 | biostudies-literature | 2015 Feb
REPOSITORIES: biostudies-literature
Publications
Protective role for caspase-11 during acute experimental murine colitis.
Oficjalska Katarzyna K Raverdeau Mathilde M Aviello Gabriella G Wade Siobhan C SC Hickey Ana A Sheehan Katherine M KM Corr Sinead C SC Kay Elaine W EW O'Neill Luke A LA Mills Kingston H G KH Creagh Emma M EM
Journal of immunology (Baltimore, Md. : 1950) 20141229 3
Activation of the noncanonical inflammasome, mediated by caspase-11, serves as an additional pathway for the production of the proinflammatory cytokines IL-1β and IL-18. Noncanonical inflammasome activity occurs during host defense against Gram-negative bacteria and in models of acute septic shock. We propose that the noncanonical inflammasome is activated in mice during acute intestinal inflammation elicited by dextran sodium sulfate (DSS), a model of experimental colitis. We find that caspase- ...[more]
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Project description:Murine 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 pro-inflammatory 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.
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