Microbiota Normalization Reveals that Canonical Caspase-1 Activation Exacerbates Chemically Induced Intestinal Inflammation.

2.50
Hdl Handle:
http://hdl.handle.net/10033/621026
Title:
Microbiota Normalization Reveals that Canonical Caspase-1 Activation Exacerbates Chemically Induced Intestinal Inflammation.
Authors:
Błażejewski, Adrian J; Thiemann, Sophie; Schenk, Alexander; Pils, Marina C; Gálvez, Eric J C; Roy, Urmi; Heise, Ulrike; de Zoete, Marcel R; Flavell, Richard A; Strowig, Till ( 0000-0003-0185-1459 )
Abstract:
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.
Affiliation:
Helmholtz Centre for infection research, Inhoffenstr. 7. 38124 Braunschweig, Germany.
Citation:
Microbiota Normalization Reveals that Canonical Caspase-1 Activation Exacerbates Chemically Induced Intestinal Inflammation. 2017, 19 (11):2319-2330 Cell Rep
Journal:
Cell reports
Issue Date:
13-Jun-2017
URI:
http://hdl.handle.net/10033/621026
DOI:
10.1016/j.celrep.2017.05.058
PubMed ID:
28614717
Type:
Article
Language:
en
ISSN:
2211-1247
Appears in Collections:
publications of the research group microbial immune regulation (MIKI); publications of the junior research group infection biology of Salmonella (IBIS); publications of the service unit animal experimentation: (TEE); publications of the department of experimental infection research ([TC] EXPI)

Full metadata record

DC FieldValue Language
dc.contributor.authorBłażejewski, Adrian Jen
dc.contributor.authorThiemann, Sophieen
dc.contributor.authorSchenk, Alexanderen
dc.contributor.authorPils, Marina Cen
dc.contributor.authorGálvez, Eric J Cen
dc.contributor.authorRoy, Urmien
dc.contributor.authorHeise, Ulrikeen
dc.contributor.authorde Zoete, Marcel Ren
dc.contributor.authorFlavell, Richard Aen
dc.contributor.authorStrowig, Tillen
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.en
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

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