Protective role for caspase-11 during acute experimental murine colitis

Katarzyna Oficjalska, Mathilde Raverdeau, Gabriella Aviello, Siobhan C Wade, Ana Hickey, Katherine M Sheehan, Sinead C Corr, Elaine W Kay, Luke A O'Neill, Kingston H G Mills, Emma M Creagh

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52 Citations (Scopus)

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 languageEnglish
Pages (from-to)1252-1260
Number of pages9
JournalThe Journal of Immunology
Volume194
Issue number3
DOIs
Publication statusPublished - 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

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  • Cite this

    Oficjalska, K., Raverdeau, M., Aviello, G., Wade, S. C., Hickey, A., Sheehan, K. M., Corr, S. C., Kay, E. W., O'Neill, L. A., Mills, K. H. G., & Creagh, E. M. (2015). Protective role for caspase-11 during acute experimental murine colitis. The Journal of Immunology, 194(3), 1252-1260. https://doi.org/10.4049/jimmunol.1400501