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

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dc.contributor.authorAllen, Irving C.en
dc.contributor.authorTeKippe, Erin McElvaniaen
dc.contributor.authorWoodford, Rita-Marie T.en
dc.contributor.authorUronis, Joshua M.en
dc.contributor.authorHoll, Eda K.en
dc.contributor.authorRogers, Arlin B.en
dc.contributor.authorHerfarth, Hans H.en
dc.contributor.authorJobin, Christianen
dc.contributor.authorTing, Jenny P.-Y.en
dc.date.accessioned2017-01-10T00:48:19Zen
dc.date.available2017-01-10T00:48:19Zen
dc.date.issued2010-05-10en
dc.description.abstractColitis-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-1&Beta; 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<sup>-l-</sup> mice showed an increase in acute and recurring colitis and CAC, although the disease outcome was less severe in Nlrp3<sup>-l-</sup> mice than in Pycard<sup>-l-</sup> or Casp1<sup>-l-</sup> animals. No significant differences were observed in disease progression or outcome in Nlrc4<sup>-l-</sup> 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.en
dc.description.versionPublished versionen
dc.format.extent1045 - 1056 (12) page(s)en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1084/jem.20100050en
dc.identifier.issn0022-1007en
dc.identifier.issue5en
dc.identifier.urihttp://hdl.handle.net/10919/74042en
dc.identifier.volume207en
dc.language.isoenen
dc.publisherRockefeller University Pressen
dc.relation.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000277452100015&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1en
dc.rightsCreative Commons Attribution-NonCommercial-ShareAlike 3.0 Unporteden
dc.rights.holderThe Author(s)en
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/en
dc.subjectImmunologyen
dc.subjectMedicine, Research & Experimentalen
dc.subjectResearch & Experimental Medicineen
dc.subjectIL-1 RECEPTOR ANTAGONISTen
dc.subjectCOLORECTAL-CANCERen
dc.subjectINTESTINAL INFLAMMATIONen
dc.subjectCOLON CARCINOGENESISen
dc.subjectNALP3 INFLAMMASOMEen
dc.subjectTUMOR PROGRESSIONen
dc.subjectCROHNS-DISEASEen
dc.subjectBOWEL-DISEASEen
dc.subjectCUTTING EDGEen
dc.subjectMOUSE MODELen
dc.titleThe NLRP3 inflammasome functions as a negative regulator of tumorigenesis during colitis-associated canceren
dc.title.serialJournal of Experimental Medicineen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/Veterinary Medicineen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/Biomedical Sciences and Pathobiologyen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/CVM T&R Facultyen

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