Lysophosphatidylcholine activates caspase-1 in microglia via a novel pathway involving two inflammasomes

•Lysophosphatidylcholine (LPC) activates caspase-1 in microglia.•Prestimulation with LPS is required for LPC-induced caspase-1 activation.•LPC-induced caspase-1 activation depends on inflammasomes NLRC4 and NLRP3.•LPC-induced caspase-1 activation requires activity of the adaptor protein ASC.

Inflammasomes regulate microglial caspase-1 activation and subsequent neuroinflammatory processes in brain pathology. In the present study, we have identified inflammasomes causing caspase-1 activation following stimulation of microglia with lysophosphatidylcholine (LPC), a proinflammatory lipid generated under pathological conditions in the brain. LPC-induced caspase-1 activation in microglia was found to depend on LPS prestimulation, inflammasome NLRP3 and adaptor molecule ASC. Furthermore, knockdown of inflammasome NLRC4 inhibited LPC-stimulated caspase-1 activity in microglia, suggesting the requirement of two inflammasomes for optimal caspase-1 activity.

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