Format

Send to:

Choose Destination
See comment in PubMed Commons below
Immunity. 2010 Mar 26;32(3):379-91. doi: 10.1016/j.immuni.2010.03.003. Epub 2010 Mar 18.

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

Author information

  • 1Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

Abstract

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.

PMID:
20303296
[PubMed - indexed for MEDLINE]
PMCID:
PMC2982187
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk