Protective Role for Caspase-11 during Acute Experimental Murine Colitis.
Item Type:Journal Article
Citation:Oficjalska K1, Raverdeau M1, Aviello G2, Wade SC1, Hickey A1, Sheehan KM3, Corr SC1, Kay EW3, O'Neill LA1, Mills KH1, Creagh EM4., Protective Role for Caspase-11 during Acute Experimental Murine Colitis., Journal of Immunology, 194, 3, 2015, 1252-1260
J Immunol-2014-Oficjalska-jimmunol.1400501(1).pdf (Published (author's copy) - Peer Reviewed) 1.986Mb
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.
Science Foundation Ireland (SFI)
Type of material:Journal Article
Series/Report no:Journal of Immunology
Availability:Full text available
Subject (TCD):Immunology, Inflammation & Infection