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Publication : A functional role for Nlrp6 in intestinal inflammation and tumorigenesis.

First Author  Chen GY Year  2011
Journal  J Immunol Volume  186
Issue  12 Pages  7187-94
PubMed ID  21543645 Mgi Jnum  J:175503
Mgi Id  MGI:5285812 Doi  10.4049/jimmunol.1100412
Citation  Chen GY, et al. (2011) A functional role for Nlrp6 in intestinal inflammation and tumorigenesis. J Immunol 186(12):7187-94
abstractText  The nucleotide-binding oligomerization domain-like receptor (NLR) family member, Nlrp6, has been implicated in inflammasome signaling to activate caspase-1, which is essential for the production of mature IL-1beta and IL-18. However, a function for Nlrp6 in vivo has never been demonstrated. Due to the relative high expression of Nlrp6 in intestinal tissue, we hypothesized that Nlrp6 has a role in intestinal homeostasis. Indeed, Nlrp6-deficient mice are more susceptible to chemically induced colitis as well as colitis-induced tumorigenesis than wild-type (WT) mice. Nlrp6-deficient mice exhibited significantly more inflammation within the colon than WT mice after dextran sulfate sodium treatment. Their inability to resolve inflammation and repair damaged epithelium as efficiently as WT mice resulted in prolonged increases in epithelial proliferative activity that likely underlie the increased propensity for tumors in these mice during chronic inflammation. We further show that the activity of Nlrp6 in hematopoietic cells is critical for protection against inflammation-related colon tumorigenesis. This study highlights the importance of NLR function in maintaining intestinal homeostasis to prevent the development of aberrant inflammation and tumor development within the colon.
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