Protective role for caspase-11 during acute experimental murine colitis.
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2015Access:
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LUKE O'NEILL, MATHILDE RAVERDEAU, KINGSTON MILLS, EMMA CREAGH, SINEAD CORR, 'Protective role for caspase-11 during acute experimental murine colitis.', 2015, Journal of immunology (Baltimore, Md. : 1950);, 194;, 3;Download Item:
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Abstract:
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-11−/− mice display enhanced susceptibility to DSS, because of impaired IL-18 production. The impaired IL-18 levels observed are shown to result in reduced intestinal epithelial cell proliferation and increased cell death. We also suggest that a novel type II IFN–dependent, type I IFN-TRIF–independent signaling pathway is required for in vivo caspase-11 production in intestinal epithelial cells during DSS colitis. Collectively, these data suggest that IFN-γ–mediated caspase-11 expression has a key role maintaining intestinal epithelial barrier integrity in vivo during experimentally induced acute colitis.
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Science Foundation Ireland
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http://people.tcd.ie/laoneillhttp://people.tcd.ie/corrsc
http://people.tcd.ie/millsk
http://people.tcd.ie/ecreagh
http://people.tcd.ie/raverdem
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Journal of immunology (Baltimore, Md. : 1950);194;
3;
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caspase-11Subject (TCD):
Immunology, Inflammation & InfectionDOI:
http://dx.doi.org/10.4049/jimmunol.140050Licences: