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

(2010) IMMUNITY. 32(3). p.379-391
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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-1 beta (IL-1 beta) 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 NIrp3 inflammasome is critically involved in the maintenance of intestinal homeostasis and protection against colitis.
Keywords
MICE DEFICIENT, CASPASE-1 INFLAMMASOMES, IL-1-BETA-CONVERTING ENZYME, CROHNS-DISEASE, INTESTINAL INFLAMMATION, ULCERATIVE-COLITIS, BOWEL-DISEASE, DEXTRAN SULFATE SODIUM, TOLL-LIKE-RECEPTORS, DOUBLE-BLIND

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Citation

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MLA
Zaki, Md Hasan et al. “The NLRP3 Inflammasome Protects Against Loss of Epithelial Integrity and Mortality During Experimental Colitis.” IMMUNITY 32.3 (2010): 379–391. Print.
APA
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.
Chicago author-date
Zaki, Md Hasan, Kelli L Boyd, Peter Vogel, Michael B Kastan, Mohamed Lamkanfi, and Thirumala-Devi Kanneganti. 2010. “The NLRP3 Inflammasome Protects Against Loss of Epithelial Integrity and Mortality During Experimental Colitis.” Immunity 32 (3): 379–391.
Chicago author-date (all authors)
Zaki, Md Hasan, Kelli L Boyd, Peter Vogel, Michael B Kastan, Mohamed Lamkanfi, and Thirumala-Devi Kanneganti. 2010. “The NLRP3 Inflammasome Protects Against Loss of Epithelial Integrity and Mortality During Experimental Colitis.” Immunity 32 (3): 379–391.
Vancouver
1.
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;32(3):379–91.
IEEE
[1]
M. H. Zaki, K. L. Boyd, P. Vogel, M. B. Kastan, M. Lamkanfi, and T.-D. Kanneganti, “The NLRP3 inflammasome protects against loss of epithelial integrity and mortality during experimental colitis,” IMMUNITY, vol. 32, no. 3, pp. 379–391, 2010.
@article{931374,
  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-1 beta (IL-1 beta) 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 NIrp3 inflammasome is critically involved in the maintenance of intestinal homeostasis and protection against colitis.},
  author       = {Zaki, Md Hasan and Boyd, Kelli L and Vogel, Peter and Kastan, Michael B and Lamkanfi, Mohamed and Kanneganti, Thirumala-Devi},
  issn         = {1074-7613},
  journal      = {IMMUNITY},
  keywords     = {MICE DEFICIENT,CASPASE-1 INFLAMMASOMES,IL-1-BETA-CONVERTING ENZYME,CROHNS-DISEASE,INTESTINAL INFLAMMATION,ULCERATIVE-COLITIS,BOWEL-DISEASE,DEXTRAN SULFATE SODIUM,TOLL-LIKE-RECEPTORS,DOUBLE-BLIND},
  language     = {eng},
  number       = {3},
  pages        = {379--391},
  title        = {The NLRP3 inflammasome protects against loss of epithelial integrity and mortality during experimental colitis},
  url          = {http://dx.doi.org/10.1016/j.immuni.2010.03.003},
  volume       = {32},
  year         = {2010},
}

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