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.
Original language | English |
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Pages (from-to) | 1252-1260 |
Number of pages | 9 |
Journal | The Journal of Immunology |
Volume | 194 |
Issue number | 3 |
DOIs | |
Publication status | Published - 1 Feb 2015 |
Keywords
- Adaptor Proteins, Vesicular Transport
- Animals
- Caspases
- Colitis
- Cytokines
- Dextran Sulfate
- Disease Models, Animal
- Gene Expression
- Genetic Predisposition to Disease
- Immunohistochemistry
- Interferon-gamma
- Intestinal Mucosa
- Mice
- Mice, Knockout
- Phenotype
- Signal Transduction
- Journal Article
- Research Support, Non-U.S. Gov't