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

Research output: Contribution to journalArticle

49 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

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Inflammasomes
Dextran Sulfate
Interleukin-18
Colitis
Caspases
Epithelial Cells
Septic Shock
Gram-Negative Bacteria
Interleukin-1
Cell Death
Theoretical Models
Cell Proliferation
Cytokines
Inflammation

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

Cite this

Oficjalska, K., Raverdeau, M., Aviello, G., Wade, S. C., Hickey, A., Sheehan, K. M., ... 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

Protective role for caspase-11 during acute experimental murine colitis. / Oficjalska, Katarzyna; Raverdeau, Mathilde; Aviello, Gabriella; Wade, Siobhan C; Hickey, Ana; Sheehan, Katherine M; Corr, Sinead C; Kay, Elaine W; O'Neill, Luke A; Mills, Kingston H G; Creagh, Emma M.

In: The Journal of Immunology, Vol. 194, No. 3, 01.02.2015, p. 1252-1260.

Research output: Contribution to journalArticle

Oficjalska, K, Raverdeau, M, Aviello, G, Wade, SC, Hickey, A, Sheehan, KM, Corr, SC, Kay, EW, O'Neill, LA, Mills, KHG & Creagh, EM 2015, 'Protective role for caspase-11 during acute experimental murine colitis', The Journal of Immunology, vol. 194, no. 3, pp. 1252-1260. https://doi.org/10.4049/jimmunol.1400501
Oficjalska K, Raverdeau M, Aviello G, Wade SC, Hickey A, Sheehan KM et al. Protective role for caspase-11 during acute experimental murine colitis. The Journal of Immunology. 2015 Feb 1;194(3):1252-1260. https://doi.org/10.4049/jimmunol.1400501
Oficjalska, Katarzyna ; Raverdeau, Mathilde ; Aviello, Gabriella ; Wade, Siobhan C ; Hickey, Ana ; Sheehan, Katherine M ; Corr, Sinead C ; Kay, Elaine W ; O'Neill, Luke A ; Mills, Kingston H G ; Creagh, Emma M. / Protective role for caspase-11 during acute experimental murine colitis. In: The Journal of Immunology. 2015 ; Vol. 194, No. 3. pp. 1252-1260.
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