title: Protective role for caspase-11 during acute experimental murine colitis.
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.
authors.affiliation: School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland;
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Oficjalska
authors.affiliation: School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland;
authors.forename: Mathilde
authors.initials: M
authors.lastname: Raverdeau
authors.affiliation: School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland; and.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Aviello
authors.affiliation: School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland;
authors.forename: Siobhan C
authors.initials: SC
authors.lastname: Wade
authors.affiliation: School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland;
authors.forename: Ana
authors.initials: A
authors.lastname: Hickey
authors.affiliation: Royal College of Surgeons in Ireland and Beaumont Hospital, Dublin 9, Ireland.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Sheehan
authors.affiliation: School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland;
authors.forename: Sinead C
authors.initials: SC
authors.lastname: Corr
authors.affiliation: Royal College of Surgeons in Ireland and Beaumont Hospital, Dublin 9, Ireland.
authors.forename: Elaine W
authors.initials: EW
authors.lastname: Kay
authors.affiliation: School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland;
authors.forename: Luke A
authors.initials: LA
authors.lastname: O'Neill
authors.affiliation: School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland;
authors.forename: Kingston H G
authors.initials: KH
authors.lastname: Mills
authors.affiliation: School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland; ecreagh@tcd.ie.
authors.forename: Emma M
authors.initials: EM
authors.lastname: Creagh
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D000818:Animals; D020169:Caspases / Q000235:genetics / Q000378:metabolism*; D053471:Caspases, Initiator; D003092:Colitis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate / Q000009:adverse effects; D004195:Disease Models, Animal; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D015398:Signal Transduction
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D020169:Caspases; D053471:Caspases, Initiator; D016207:Cytokines; D016264:Dextran Sulfate; D007371:Interferon-gamma; C476286:Ticam1 protein, mouse; C101136:Casp4 protein, mouse