TY - JOUR
T1 - The NOD-Like Receptor NLRP12 Attenuates Colon Inflammation and Tumorigenesis
AU - Zaki, Md Hasan
AU - Vogel, Peter
AU - Malireddi, R. K Subbarao
AU - Body-Malapel, Mathilde
AU - Anand, Paras K
AU - Bertin, John
AU - Green, Douglas R
AU - Lamkanfi, Mohamed
AU - Kanneganti, Thirumala Devi
N1 - Funding Information:
We thank Anthony Coyle, Ethan Grant, John Bertin (Millennium Pharmaceuticals), Gabriel Nuñez (University of Michigan), and Richard Flavell (Yale) for generous supply of mutant mice. M.H.Z is supported by Gephardt fellowship. M.L. is supported by grants from the European Union Framework Program 7 (Marie-Curie Grant 256432) and the Fund for Scientific Research-Flanders. This work was supported by National Institute of Health Grants (R01AR056296 and AI088177), and the American Lebanese Syrian Associated Charities (ALSAC) to T.-D.K.
PY - 2011/11/15
Y1 - 2011/11/15
N2 - NLRP12 is a member of the intracellular Nod-like receptor (NLR) family that has been suggested to downregulate the production of inflammatory cytokines, but its physiological role in regulating inflammation has not been characterized. We analyzed mice deficient in Nlrp12 to study its role in inflammatory diseases such as colitis and colorectal tumorigenesis. We show that Nlrp12-deficient mice are highly susceptible to colon inflammation and tumorigenesis, which is associated with increased production of inflammatory cytokines, chemokines, and tumorigenic factors. Enhanced colon inflammation and colorectal tumor development in Nlrp12-deficient mice are due to a failure to dampen NF-κB and ERK activation in macrophages. These results reveal a critical role for NLRP12 in maintaining intestinal homeostasis and providing protection against colorectal tumorigenesis.
AB - NLRP12 is a member of the intracellular Nod-like receptor (NLR) family that has been suggested to downregulate the production of inflammatory cytokines, but its physiological role in regulating inflammation has not been characterized. We analyzed mice deficient in Nlrp12 to study its role in inflammatory diseases such as colitis and colorectal tumorigenesis. We show that Nlrp12-deficient mice are highly susceptible to colon inflammation and tumorigenesis, which is associated with increased production of inflammatory cytokines, chemokines, and tumorigenic factors. Enhanced colon inflammation and colorectal tumor development in Nlrp12-deficient mice are due to a failure to dampen NF-κB and ERK activation in macrophages. These results reveal a critical role for NLRP12 in maintaining intestinal homeostasis and providing protection against colorectal tumorigenesis.
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U2 - 10.1016/j.ccr.2011.10.022
DO - 10.1016/j.ccr.2011.10.022
M3 - Article
C2 - 22094258
AN - SCOPUS:81255189478
SN - 1535-6108
VL - 20
SP - 649
EP - 660
JO - Cancer Cell
JF - Cancer Cell
IS - 5
ER -