Lysosome rupture triggers NLRP3 inflammasome activation in macrophages. However, the underlying mechanism is not fully understood. Here, we showed that the TAK1-JNK pathway, a MAPK signaling pathway, is activated through lysosome rupture, and this activation is necessary for the complete activation of the NLRP3 inflammasome through the oligomerization of an adapter protein, ASC. We also revealed that the activation of the TAK1-JNK pathway is sustained through Ca2+ ions, and CaMKII functions upstream of the TAK1-JNK pathway and specifically regulates lysosome rupture-induced NLRP3 inflammasome activation. These data suggested a novel role for the TAK1-JNK pathway as a critical regulator of NLRP3 inflammasome activation.
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