Control of intestinal homeostasis, colitis, and colitis-associated colorectal cancer by the inflammatory caspases
- PMID: 20226691
- DOI: 10.1016/j.immuni.2010.02.012
Control of intestinal homeostasis, colitis, and colitis-associated colorectal cancer by the inflammatory caspases
Abstract
Inflammatory caspases are essential effectors of inflammation and cell death. Here, we investigated their roles in colitis and colorectal cancer and report a bimodal regulation of intestinal homeostasis, inflammation and tumorigenesis by caspases-1 and -12. Casp1(-/-) mice exhibited defects in mucosal tissue repair and succumbed rapidly after dextran sulfate sodium administration. This phenotype was rescued by administration of exogenous interleukin-18 and was partially reproduced in mice deficient in the inflammasome adaptor ASC. Casp12(-/-) mice, in which the inflammasome is derepressed, were resistant to acute colitis and showed signs of enhanced repair. Together with their increased inflammatory response, the enhanced repair response of Casp12(-/-) mice rendered them more susceptible to colorectal cancer induced by azoxymethane (AOM)+DSS. Taken together, our results indicate that the inflammatory caspases are critical in the induction of inflammation in the gut after injury, which is necessary for tissue repair and maintenance of immune tolerance.
Comment in
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Interleukin-18 in intestinal inflammation: friend and foe?Immunity. 2010 Mar 26;32(3):300-2. doi: 10.1016/j.immuni.2010.03.010. Immunity. 2010. PMID: 20346770
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Mucosal immunology: Inflammasome activation in the gut.Nat Rev Immunol. 2010 May;10(5):293. doi: 10.1038/nri2776. Nat Rev Immunol. 2010. PMID: 20425920 No abstract available.
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