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

ABSTRACT: Interleukin-1? (IL-1?) 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-1? production in microglial cells. We used a combination of in vitro (Bv2 microglial cell cultures) and in vivo (mice injected with amyloid-? (A?)) techniques to address the role of caspase-1 activation in release of IL-1?. DAPK1 involvement was postulated through genetic approaches and pharmacological blockade of this enzyme. We found that A?_25-35 stimulation induced IL-1? production and caspase-1 activation in LPS-primed Bv2 cells and mice. DAPK1 knockdown and catalytic activity inhibition reduced IL-1? maturation and caspase-1 activation, nevertheless, DAPK1 overexpression attenuated these effects. A?_25-35-induced lysosomal cathepsin B leakage was required for DAPK1 activation. Furthermore, repeated DAPK1 inhibitor treatment ameliorated the memory impairment in A?_25-35-injected mice. Taken together, our findings suggest that DAPK1 facilitates A?_25-35-induced IL-1? production through regulating caspase-1 activation in microglial cells.

SUBMITTER: Song L 

PROVIDER: S-EPMC6028446 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature