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The NLRP3 inflammasome functions as a negative regulator of tumorigenesis during colitis-associated cancer.

Publication ,  Journal Article
Allen, IC; TeKippe, EM; Woodford, R-MT; Uronis, JM; Holl, EK; Rogers, AB; Herfarth, HH; Jobin, C; Ting, JP-Y
Published in: J Exp Med
May 10, 2010

Colitis-associated cancer (CAC) is a major complication of inflammatory bowel diseases. We show that components of the inflammasome are protective during acute and recurring colitis and CAC in the dextran sulfate sodium (DSS) and azoxymethane + DSS models. Mice lacking the inflammasome adaptor protein PYCARD (ASC) and caspase-1 demonstrate increased disease outcome, morbidity, histopathology, and polyp formation. The increased tumor burden is correlated with attenuated levels of IL-1beta and IL-18 at the tumor site. To decipher the nucleotide-binding domain, leucine-rich-repeat-containing (NLR) component that is involved in colitis and CAC, we assessed Nlrp3 and Nlrc4 deficient mice. Nlrp3(-/-) mice showed an increase in acute and recurring colitis and CAC, although the disease outcome was less severe in Nlrp3(-/-) mice than in Pycard(-/-) or Casp1(-/-) animals. No significant differences were observed in disease progression or outcome in Nlrc4(-/-) mice compared with similarly treated wild-type animals. Bone marrow reconstitution experiments show that Nlrp3 gene expression and function in hematopoietic cells, rather than intestinal epithelial cells or stromal cells, is responsible for protection against increased tumorigenesis. These data suggest that the inflammasome functions as an attenuator of colitis and CAC.

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Published In

J Exp Med

DOI

EISSN

1540-9538

Publication Date

May 10, 2010

Volume

207

Issue

5

Start / End Page

1045 / 1056

Location

United States

Related Subject Headings

  • Tumor Burden
  • Neoplasms
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Mice, Knockout
  • Mice
  • Interleukin-1beta
  • Interleukin-18
  • Inflammatory Bowel Diseases
  • Immunology
  • Humans
 

Citation

APA
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MLA
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Allen, I. C., TeKippe, E. M., Woodford, R.-M., Uronis, J. M., Holl, E. K., Rogers, A. B., … Ting, J.-Y. (2010). The NLRP3 inflammasome functions as a negative regulator of tumorigenesis during colitis-associated cancer. J Exp Med, 207(5), 1045–1056. https://doi.org/10.1084/jem.20100050
Allen, Irving C., Erin McElvania TeKippe, Rita-Marie T. Woodford, Joshua M. Uronis, Eda K. Holl, Arlin B. Rogers, Hans H. Herfarth, Christian Jobin, and Jenny P-Y Ting. “The NLRP3 inflammasome functions as a negative regulator of tumorigenesis during colitis-associated cancer.J Exp Med 207, no. 5 (May 10, 2010): 1045–56. https://doi.org/10.1084/jem.20100050.
Allen IC, TeKippe EM, Woodford R-MT, Uronis JM, Holl EK, Rogers AB, et al. The NLRP3 inflammasome functions as a negative regulator of tumorigenesis during colitis-associated cancer. J Exp Med. 2010 May 10;207(5):1045–56.
Allen, Irving C., et al. “The NLRP3 inflammasome functions as a negative regulator of tumorigenesis during colitis-associated cancer.J Exp Med, vol. 207, no. 5, May 2010, pp. 1045–56. Pubmed, doi:10.1084/jem.20100050.
Allen IC, TeKippe EM, Woodford R-MT, Uronis JM, Holl EK, Rogers AB, Herfarth HH, Jobin C, Ting JP-Y. The NLRP3 inflammasome functions as a negative regulator of tumorigenesis during colitis-associated cancer. J Exp Med. 2010 May 10;207(5):1045–1056.

Published In

J Exp Med

DOI

EISSN

1540-9538

Publication Date

May 10, 2010

Volume

207

Issue

5

Start / End Page

1045 / 1056

Location

United States

Related Subject Headings

  • Tumor Burden
  • Neoplasms
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Mice, Knockout
  • Mice
  • Interleukin-1beta
  • Interleukin-18
  • Inflammatory Bowel Diseases
  • Immunology
  • Humans