Mycoplasma hyorhinis activates the NLRP3 inflammasome and promotes migration and invasion of gastric cancer cells.
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)-1β and IL-18, is also involved in tumorigenesis and metastasis of various cancers.


RESULTS
To clarify whether M.hy promoted tumor development via inflammasome activation, we analyzed monocytes for IL-1β and IL-18 production upon M.hy challenge. When exposed to M.hy, human monocytes exhibited rapid and robust IL-1β and IL-18 secretion. We further identified that lipid-associated membrane protein (LAMP) from M.hy was responsible for IL-1β induction. Applying competitive inhibitors, gene specific shRNA and gene targeted mice, we verified that M.hy induced IL-1β 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-1β 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.
Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Yongfen
Y
Xu
Hua
H
Li
Wei
W
Chen
Xiaomin
X
Yao
Yue
Y
Xing
Xun
X
Wang
Jin
J
Zhong
Guangxun
G
Meng
D000818:Animals; D001426:Bacterial Proteins / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D020382:Interleukin-18 / Q000096:biosynthesis; D053583:Interleukin-1beta / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009175:Mycoplasma Infections / Q000276:immunology*; D045790:Mycoplasma hyorhinis / Q000276:immunology / Q000502:physiology*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009361:Neoplasm Invasiveness; D013274:Stomach Neoplasms / Q000276:immunology / Q000382:microbiology / Q000473:pathology*
D001426:Bacterial Proteins; D002352:Carrier Proteins; C000589760:IL18 protein, human; D058847:Inflammasomes; D020382:Interleukin-18; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human