IL-18 induced IL-23/IL-17 expression impairs Aβ clearance in cultured THP-1 and BV2 cells.

Recent studies have provided overwhelming evidence of the involvement of microglia-related molecular networks in the pathogenesis of Alzheimer's diseases (AD). The potential involvement of pro-inflammatory cytokines interleukin (IL)-18, IL-23 and IL-17 on amyloid (Aβ) clearance is still unclear. In this study, we addressed that there might be a net relationship among IL-18, IL-23, and IL-17 and they can affect Aβ clearance in cultured macrophage/microglia cells. In human macrophage cell line THP-1, Aβ42 incubation could increase the expression of IL-18, IL-23 and IL-17 in a concentration dependent manner. THP-1 cell could clear Aβ42 in the culture medium time-dependently, but its capacity of Aβ clearance was impaired by IL-18, IL-23 or IL-17 treatment. Similarly, the capacity of the microglia cell line BV2 to clear Aβ42 was impaired by IL-18, IL-23 or IL-17 treatment. In co-cultures of BV2 with APP/PS1 neuron, Aβ was efficiently cleared by BV2 cell, but Aβ clearance was impaired by IL-18, IL-23 or IL-17 treatment. The effects of IL-18, IL-23 and IL-17 could be blocked by their corresponding neutralizing antibodies. In addition, the inhibitory effects of IL-18 were blocked by IL-23 or IL-17 neutralizing antibodies while the inhibitory effects of IL-23 were blocked by IL-17 neutralizing antibodies. Our study provides evidences showing that amyloid induced IL-18/IL-23/IL-17 axis could impair macrophage and microglia-mediated Aβ clearance. Thus, IL-18/IL-23/IL-17 axis might be a therapeutic target in AD.