The NLRP3 inflammasome protects against loss of epithelial integrity and mortality during experimental colitis.

Published

Journal Article

Decreased expression of the Nlrp3 protein is associated with susceptibility to Crohn's disease. However, the role of Nlrp3 in colitis has not been characterized. Nlrp3 interacts with the adaptor protein ASC to activate caspase-1 in inflammasomes, which are protein complexes responsible for the maturation and secretion of interleukin-1beta (IL-1beta) and IL-18. Here, we showed that mice deficient for Nlrp3 or ASC and caspase-1 were highly susceptible to dextran sodium sulfate (DSS)-induced colitis. Defective inflammasome activation led to loss of epithelial integrity, resulting in systemic dispersion of commensal bacteria, massive leukocyte infiltration, and increased chemokine production in the colon. This process was a consequence of a decrease in IL-18 in mice lacking components of the Nlrp3 inflammasome, resulting in higher mortality rates. Thus, the Nlrp3 inflammasome is critically involved in the maintenance of intestinal homeostasis and protection against colitis.

Full Text

Duke Authors

Cited Authors

  • Zaki, MH; Boyd, KL; Vogel, P; Kastan, MB; Lamkanfi, M; Kanneganti, T-D

Published Date

  • March 26, 2010

Published In

Volume / Issue

  • 32 / 3

Start / End Page

  • 379 - 391

PubMed ID

  • 20303296

Pubmed Central ID

  • 20303296

Electronic International Standard Serial Number (EISSN)

  • 1097-4180

Digital Object Identifier (DOI)

  • 10.1016/j.immuni.2010.03.003

Language

  • eng

Conference Location

  • United States