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 |
|---|---|
| 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 |
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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
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 journal › Article
}
TY - JOUR
T1 - Protective role for caspase-11 during acute experimental murine colitis
AU - Oficjalska, Katarzyna
AU - Raverdeau, Mathilde
AU - Aviello, Gabriella
AU - Wade, Siobhan C
AU - Hickey, Ana
AU - Sheehan, Katherine M
AU - Corr, Sinead C
AU - Kay, Elaine W
AU - O'Neill, Luke A
AU - Mills, Kingston H G
AU - Creagh, Emma M
N1 - Copyright © 2015 The Authors.
PY - 2015/2/1
Y1 - 2015/2/1
N2 - 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.
AB - 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.
KW - Adaptor Proteins, Vesicular Transport
KW - Animals
KW - Caspases
KW - Colitis
KW - Cytokines
KW - Dextran Sulfate
KW - Disease Models, Animal
KW - Gene Expression
KW - Genetic Predisposition to Disease
KW - Immunohistochemistry
KW - Interferon-gamma
KW - Intestinal Mucosa
KW - Mice
KW - Mice, Knockout
KW - Phenotype
KW - Signal Transduction
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.4049/jimmunol.1400501
DO - 10.4049/jimmunol.1400501
M3 - Article
C2 - 25548224
VL - 194
SP - 1252
EP - 1260
JO - The Journal of Immunology
JF - The Journal of Immunology
SN - 0022-1767
IS - 3
ER -