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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Allen, IC; TeKippe, EM; Woodford, R-MT; Uronis, JM; Holl, EK; Rogers, AB; Herfarth, HH; Jobin, C; Ting, JP-Y

Published Date

  • May 10, 2010

Published In

Volume / Issue

  • 207 / 5

Start / End Page

  • 1045 - 1056

PubMed ID

  • 20385749

Pubmed Central ID

  • 20385749

Electronic International Standard Serial Number (EISSN)

  • 1540-9538

Digital Object Identifier (DOI)

  • 10.1084/jem.20100050

Language

  • eng

Conference Location

  • United States