Analyses of molecular mechanism for regulating gene expression of anti-inflammatory NLR family member PYNOD

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590374
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Kanazawa University
• Principal Investigator: IMAMURA Ryu 金沢大学, がん進展制御研究所, 助教 (10311680)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: NLRファミリー / 自然免疫 / PYNOD / 胃がん / 遺伝子発現

Outline of Final Research Achievements

Many members of the nucleotide-binding and oligomerization domain (NOD) and leucine-rich-repeat (LRR)-containing protein (NLR) family play important roles in pathogen recognition and inflammation. We identified PYNOD/NLRP10, one of the member of this family that lacks LRR, and found that PYNOD inhibit inflammatory signal mediated by caspase-1 and ASC. To further investigate physiological function of PYNOD, we have established PYNOD-deficient mice. PYNOD-deficient mice exhibited no obvious gross abnormalities, no evidence of autoimmunity and spontaneous tumor formation, and normal innate immune responses.
However, we have found that PYNOD is highly expressed in stomach of gastric cancer mouse model (Gan mice), in which inflammatory COX-2/PGE2 pathway and Wnt signaling are activated simultaneously in gastric mucosa. Furthermore, we also detected high PYNOD expression in tumor region containing papillary type adenocarcinoma from gastric cancer patients.

Free Research Field

免疫学