Ana Hickey

Elaine W. Kay

Emma M. Creagh

Gabriella Aviello

Katarzyna Oficjalska

Katherine M. Sheehan

Kingston H. G. Mills

Luke A. O’Neill

Mathilde Raverdeau

Pizarro

Sinead C. Corr

Siobhan C. Wade

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.</jats:p

Crossref

The Journal of Immunology

Protective Role for Caspase-11 during Acute Experimental Murine Colitis

Protective Role for Caspase-11 during Acute Experimental Murine Colitis

Abstract

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