Death-associated protein kinase 1 mediates interleukin-1β production through regulating inlfammasome activation in Bv2 microglial cells and mice

Interleukin-1β (IL-1β) plays a crucial role in mediating inflammation and innate immunity response in the central nervous system. Death-associated protein kinase 1 (DAPK1) was shown to be involved in several cellular processes. Here, we investigated the effects of DAPK1 on IL-1β production in microglial cells. We used a combination of in vitro (Bv2 microglial cell cultures) and in vivo (mice injected with amyloid-β (Aβ)) techniques to address the role of caspase-1 activation in release of IL-1β. DAPK1 involvement was postulated through genetic approaches and pharmacological blockade of this enzyme. We found that Aβ25–35 stimulation induced IL-1β production and caspase-1 activation in LPS-primed Bv2 cells and mice. DAPK1 knockdown and catalytic activity inhibition reduced IL-1β maturation and caspase-1 activation, nevertheless, DAPK1 overexpression attenuated these effects. Aβ25–35-induced lysosomal cathepsin B leakage was required for DAPK1 activation. Furthermore, repeated DAPK1 inhibitor treatment ameliorated the memory impairment in Aβ25–35-injected mice. Taken together, our findings suggest that DAPK1 facilitates Aβ25–35-induced IL-1β production through regulating caspase-1 activation in microglial cells.