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IL-18 production downstream of the Nlrp3 inflammasome confers protection against colorectal tumor formation

(2010) JOURNAL OF IMMUNOLOGY. 185(8). p.4912-4920
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Abstract
Colorectal cancer is a leading cause of cancer-related deaths worldwide. Chronic inflammation is recognized as a predisposing factor for the development of colon cancer, but the molecular mechanisms linking inflammation and tumorigenesis have remained elusive. Recent studies revealed a crucial role for the NOD-like receptor protein Nlrp3 in regulating inflammation through the assembly of proinflammatory protein complexes termed inflammasomes. However, its role in colorectal tumor formation remains unclear. In this study, we showed that mice deficient for Nlrp3 or the inflammasome effector caspase-1 were highly susceptible to azoxymethane/dextran sodium sulfate-induced inflammation and suffered from dramatically increased tumor burdens in the colon. This was a consequence of markedly reduced IL-18 levels in mice lacking components of the Nlrp3 inflammasome, which led to impaired production and activation of the tumor suppressors IFN-gamma and STAT1, respectively. Thus, IL-18 production downstream of the Nlrp3 inflammasome is critically involved in protection against colorectal tumorigenesis.
Keywords
TOLL-LIKE-RECEPTORS, GAMMA-INDUCING FACTOR, MEDIATES IFN-GAMMA, INTERFERON-GAMMA, CROHNS-DISEASE, ULCERATIVE-COLITIS, BOWEL-DISEASE, CELL LINE, JAK-STAT, KAPPA-B

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Citation

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Chicago
Zaki, Mohammad Hasan, Peter Vogel, Mathilde Body-Malapel, Mohamed Lamkanfi, and Thirumala-Devi Kanneganti. 2010. “IL-18 Production Downstream of the Nlrp3 Inflammasome Confers Protection Against Colorectal Tumor Formation.” Journal of Immunology 185 (8): 4912–4920.
APA
Zaki, Mohammad Hasan, Vogel, P., Body-Malapel, M., Lamkanfi, M., & Kanneganti, T.-D. (2010). IL-18 production downstream of the Nlrp3 inflammasome confers protection against colorectal tumor formation. JOURNAL OF IMMUNOLOGY, 185(8), 4912–4920.
Vancouver
1.
Zaki MH, Vogel P, Body-Malapel M, Lamkanfi M, Kanneganti T-D. IL-18 production downstream of the Nlrp3 inflammasome confers protection against colorectal tumor formation. JOURNAL OF IMMUNOLOGY. 2010;185(8):4912–20.
MLA
Zaki, Mohammad Hasan, Peter Vogel, Mathilde Body-Malapel, et al. “IL-18 Production Downstream of the Nlrp3 Inflammasome Confers Protection Against Colorectal Tumor Formation.” JOURNAL OF IMMUNOLOGY 185.8 (2010): 4912–4920. Print.
@article{1062774,
  abstract     = {Colorectal cancer is a leading cause of cancer-related deaths worldwide. Chronic inflammation is recognized as a predisposing factor for the development of colon cancer, but the molecular mechanisms linking inflammation and tumorigenesis have remained elusive. Recent studies revealed a crucial role for the NOD-like receptor protein Nlrp3 in regulating inflammation through the assembly of proinflammatory protein complexes termed inflammasomes. However, its role in colorectal tumor formation remains unclear. In this study, we showed that mice deficient for Nlrp3 or the inflammasome effector caspase-1 were highly susceptible to azoxymethane/dextran sodium sulfate-induced inflammation and suffered from dramatically increased tumor burdens in the colon. This was a consequence of markedly reduced IL-18 levels in mice lacking components of the Nlrp3 inflammasome, which led to impaired production and activation of the tumor suppressors IFN-gamma and STAT1, respectively. Thus, IL-18 production downstream of the Nlrp3 inflammasome is critically involved in protection against colorectal tumorigenesis.},
  author       = {Zaki, Mohammad Hasan and Vogel, Peter and Body-Malapel, Mathilde and Lamkanfi, Mohamed and Kanneganti, Thirumala-Devi},
  issn         = {0022-1767},
  journal      = {JOURNAL OF IMMUNOLOGY},
  keyword      = {TOLL-LIKE-RECEPTORS,GAMMA-INDUCING FACTOR,MEDIATES IFN-GAMMA,INTERFERON-GAMMA,CROHNS-DISEASE,ULCERATIVE-COLITIS,BOWEL-DISEASE,CELL LINE,JAK-STAT,KAPPA-B},
  language     = {eng},
  number       = {8},
  pages        = {4912--4920},
  title        = {IL-18 production downstream of the Nlrp3 inflammasome confers protection against colorectal tumor formation},
  url          = {http://dx.doi.org/10.4049/jimmunol.1002046},
  volume       = {185},
  year         = {2010},
}

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