114548

NLRP3

NLR family, pyrin domain containing 3;NLRP3;NLR family, pyrin domain containing 3

NACHT domain-, leucine-rich repeat-, and PYD-containing protein 3|NACHT, LRR and PYD containing protein 3|NACHT, LRR and PYD domains-containing protein 3|PYRIN-containing APAF1-like protein 1|caterpiller protein 1.1|cold autoinflammatory syndrome 1 protei

1q44

protein-coding

BACKGROUND: Mycoplasma hyorhinis (M.hyorhinis, M.hy) is associated with development of gastric and prostate cancers. The NLRP3 inflammasome, a protein complex controlling maturation of important pro-inflammatory cytokines interleukin (IL)-1beta and IL-18, is also involved in tumorigenesis and metastasis of various cancers. METHODOLOGY/PRINCIPAL FINDINGS: To clarify whether M.hy promoted tumor development via inflammasome activation, we analyzed monocytes for IL-1beta and IL-18 production upon M.hy challenge. When exposed to M.hy, human monocytes exhibited rapid and robust IL-1beta and IL-18 secretion. We further identified that lipid-associated membrane protein (LAMP) from M.hy was responsible for IL-1beta induction. Applying competitive inhibitors, gene specific shRNA and gene targeted mice, we verified that M.hy induced IL-1beta secretion was NLRP3-dependent in vitro and in vivo. Cathepsin B activity, K(+) efflux, Ca(2+) influx and ROS production were all required for the NLRP3 inflammasome activation by M.hy. Importantly, it is IL-1beta but not IL-18 produced from macrophages challenged with M.hy promoted gastric cancer cell migration and invasion. CONCLUSIONS: Our data suggest that activation of the NLRP3 inflammasome by M.hy may be associated with its promotion of gastric cancer metastasis, and anti-M.hy therapy or limiting NLRP3 signaling could be effective approach for control of gastric cancer progress.