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dc.contributor.authorBłażejewski, Adrian J
dc.contributor.authorThiemann, Sophie
dc.contributor.authorSchenk, Alexander
dc.contributor.authorPils, Marina C
dc.contributor.authorGálvez, Eric J C
dc.contributor.authorRoy, Urmi
dc.contributor.authorHeise, Ulrike
dc.contributor.authorde Zoete, Marcel R
dc.contributor.authorFlavell, Richard A
dc.contributor.authorStrowig, Till
dc.date.accessioned2017-08-01T13:20:36Z
dc.date.available2017-08-01T13:20:36Z
dc.date.issued2017-06-13
dc.identifier.citationMicrobiota Normalization Reveals that Canonical Caspase-1 Activation Exacerbates Chemically Induced Intestinal Inflammation. 2017, 19 (11):2319-2330 Cell Repen
dc.identifier.issn2211-1247
dc.identifier.pmid28614717
dc.identifier.doi10.1016/j.celrep.2017.05.058
dc.identifier.urihttp://hdl.handle.net/10033/621026
dc.description.abstractInflammasomes 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.
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleMicrobiota Normalization Reveals that Canonical Caspase-1 Activation Exacerbates Chemically Induced Intestinal Inflammation.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research, Inhoffenstr. 7. 38124 Braunschweig, Germany.en
dc.identifier.journalCell reportsen
refterms.dateFOA2018-06-12T17:48:52Z
html.description.abstractInflammasomes 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.


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