The transient receptor potential melastatin-2 (TRPM2) channel and inflammation (original) (raw)
Inflammation is an early mechanism of the immune system to eliminate pathogens and to repair damaged tissue. However, unregulated and persistent inflammation can lead to chronic inflammatory diseases. The transient receptor potential melastatin-2 (TRPM2) channel, a calcium (Ca2+)-permeable channel containing intracellular adenosine diphosphate ribose (ADPR) pyrohydrolase activity, has recently been identified as a critical molecular mechanism in reactive oxygen species (ROS)-induced inflammatory process, and thereby, emerged as a potential target for therapeutic intervention. ADPR biding to TRPM2 Nudix-like domain (or NUDT9 homology domain) results in the channel pore opening allowing lysosomal Ca2+ release and Ca2+ influx into the cells. Ca2+ influx via TRPM2 controls ROS-induced nuclear translocation of NF-κB and CXCL2 production in monocytes during inflammation in a chronic experimental colitis mouse model. Moreover, TRPM2 deficient-dendritic cells show defective Ca2+ signals and...
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