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Protective role for caspase-11 during acute experimental murine colitis.
O'NEILL, LUKE; RAVERDEAU, MATHILDE; MILLS, KINGSTON; CREAGH, EMMA; CORR, SINEAD
Activation of the noncanonical inflammasome, mediated by caspase-11, serves as an additional pathway for the production of the proinflammatory cytokines IL-1? 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-??mediated caspase-11 expression has a key role maintaining intestinal epithelial barrier integrity in vivo during experimentally induced acute colitis.
Keyword(s): caspase-11; Immunology, Inflammation & Infection
Publication Date:
2015
Type: Journal article
Peer-Reviewed: Yes
Language(s): English
Institution: Trinity College Dublin
Funder(s): Science Foundation Ireland
Citation(s): 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;
First Indexed: 2016-09-28 05:56:17 Last Updated: 2020-10-30 07:49:11