TGF-β induced by interleukin-34-stimulated microglia regulates microglial proliferation and attenuates oligomeric amyloid β neurotoxicity.

Microglia play critical roles in the pathogenesis of Alzheimer's disease (AD). We have previously shown that interleukin-34 (IL-34) enhances microglial proliferation and induces microglial neuroprotective properties against oligomeric amyloid β (oAβ) toxicity by producing insulin degrading enzyme, an Aβ degrading enzyme, and anti-oxidant enzyme heme oxygenase-1. In this study, we found that IL-34 dose-dependently induces TGF-β in microglia, and that TGF-β attenuates oAβ neurotoxicity in neuron microglial co-cultures. The TGF-β 1 receptor kinase inhibitor SD208 enhances microglial proliferation by IL-34 and suppresses the neuroprotective effect of IL-34-treated microglia. These findings suggest that TGF-β produced by IL-34-treated microglia is a negative regulator of microglial proliferation and enhances the neuroprotective property of microglia.