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

Publication ,  Journal Article
Zaki, MH; Boyd, KL; Vogel, P; Kastan, MB; Lamkanfi, M; Kanneganti, T-D
Published in: Immunity
March 26, 2010

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.

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Published In

Immunity

DOI

EISSN

1097-4180

Publication Date

March 26, 2010

Volume

32

Issue

3

Start / End Page

379 / 391

Location

United States

Related Subject Headings

  • Signal Transduction
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Intestinal Absorption
  • Interleukin-18
  • Immunology
  • Epithelial Cells
  • Disease Models, Animal
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Zaki, M. H., Boyd, K. L., Vogel, P., Kastan, M. B., Lamkanfi, M., & Kanneganti, T.-D. (2010). The NLRP3 inflammasome protects against loss of epithelial integrity and mortality during experimental colitis. Immunity, 32(3), 379–391. https://doi.org/10.1016/j.immuni.2010.03.003
Zaki, Md Hasan, Kelli L. Boyd, Peter Vogel, Michael B. Kastan, Mohamed Lamkanfi, and Thirumala-Devi Kanneganti. “The NLRP3 inflammasome protects against loss of epithelial integrity and mortality during experimental colitis.Immunity 32, no. 3 (March 26, 2010): 379–91. https://doi.org/10.1016/j.immuni.2010.03.003.
Zaki MH, Boyd KL, Vogel P, Kastan MB, Lamkanfi M, Kanneganti T-D. The NLRP3 inflammasome protects against loss of epithelial integrity and mortality during experimental colitis. Immunity. 2010 Mar 26;32(3):379–91.
Zaki, Md Hasan, et al. “The NLRP3 inflammasome protects against loss of epithelial integrity and mortality during experimental colitis.Immunity, vol. 32, no. 3, Mar. 2010, pp. 379–91. Pubmed, doi:10.1016/j.immuni.2010.03.003.
Zaki MH, Boyd KL, Vogel P, Kastan MB, Lamkanfi M, Kanneganti T-D. The NLRP3 inflammasome protects against loss of epithelial integrity and mortality during experimental colitis. Immunity. 2010 Mar 26;32(3):379–391.
Journal cover image

Published In

Immunity

DOI

EISSN

1097-4180

Publication Date

March 26, 2010

Volume

32

Issue

3

Start / End Page

379 / 391

Location

United States

Related Subject Headings

  • Signal Transduction
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Intestinal Absorption
  • Interleukin-18
  • Immunology
  • Epithelial Cells
  • Disease Models, Animal