Enhanced production of pro-inflammatory cytokines by inflammasome activation in microglia has been shown to induce neuronal damage in Alzheimer's disease (AD). Impairment of neurogenesis has been also shown to contribute to cognitive decline in AD. Recent reports showed that inflammasome activation is induced in mouse neural progenitor cells (NPC). Thus, we determined involvement of inflammasome activation on proliferation or differentiation of NPC. Activation of inflammasomes in NPC was examined by the expression of inflammasome components (NLRP3, ASC, or caspase-1), IL-1beta, or IL-18. Proliferation of NPC was examined by MTT assay. The differentiation potential of NPC into neural cells was evaluated by NeuN expression using western blot analysis. Stimulation with TNFalpha and LPS induced inflammasome activation and production of IL-1beta and IL-18 in mouse NPC. Stimulation with TNFalpha and LPS significantly inhibited the proliferation of NPC and NeuN expression in the differentiated NPC. The treatment with either IL-1beta or IL-18 significantly inhibited NeuN expression in the cells. Thus, the inflammasome activation may inhibit proliferation and neural differentiation in mouse NPC via the enhanced production of IL-1beta or IL-18.

To: 要旨(抄録)