The NOD-Like Receptor NLRP12 Attenuates Colon Inflammation and Tumorigenesis

Md  Hasan Zaki, Peter Vogel, R. K  Subbarao Malireddi, Mathilde Body-Malapel, Paras K Anand, John Bertin, Douglas R Green, Mohamed Lamkanfi, Thirumala Devi Kanneganti

Research output: Contribution to journalArticle

237 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)649-660
Number of pages12
JournalCancer Cell
Volume20
Issue number5
DOIs
StatePublished - Nov 15 2011

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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    Zaki, M. H., Vogel, P., Malireddi, R. K. S., Body-Malapel, M., Anand, PK., Bertin, J., Green, DR., Lamkanfi, M., & Kanneganti, T. D. (2011). The NOD-Like Receptor NLRP12 Attenuates Colon Inflammation and Tumorigenesis. Cancer Cell, 20(5), 649-660. https://doi.org/10.1016/j.ccr.2011.10.022