| First Author | Błażejewski AJ | Year | 2017 |
| Journal | Cell Rep | Volume | 19 |
| Issue | 11 | Pages | 2319-2330 |
| PubMed ID | 28614717 | Mgi Jnum | J:251828 |
| Mgi Id | MGI:6103526 | Doi | 10.1016/j.celrep.2017.05.058 |
| Citation | Blazejewski AJ, et al. (2017) Microbiota Normalization Reveals that Canonical Caspase-1 Activation Exacerbates Chemically Induced Intestinal Inflammation. Cell Rep 19(11):2319-2330 |
| abstractText | Inflammasomes play a central role in regulating intestinal barrier function and immunity during steady state and disease. Because the discoveries of a passenger mutation and a colitogenic microbiota in the widely used caspase-1-deficient mouse strain have cast doubt on previously identified direct functions of caspase-1, we reassessed the role of caspase-1 in the intestine. To this end, we generated Casp1(-/-) and Casp11(-/-) mice and rederived them into an enhanced barrier facility to standardize the microbiota. We found that caspase-11 does not influence caspase-1-dependent processing of IL-18 in homeostasis and during DSS colitis. Deficiency of caspase-1, but not caspase-11, ameliorated the severity of DSS colitis independent of microbiota composition. Ablation of caspase-1 in intestinal epithelial cells was sufficient to protect mice against DSS colitis. Moreover, Casp1(-/-) mice developed fewer inflammation-induced intestinal tumors than control mice. These data show that canonical inflammasome activation controls caspase-1 activity, contributing to exacerbation of chemical-induced colitis. |
