title: TGF-β induced by interleukin-34-stimulated microglia regulates microglial proliferation and attenuates oligomeric amyloid β neurotoxicity.
abstract: 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.
authors.affiliation: Department of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
authors.forename: Di
authors.initials: D
authors.lastname: Ma
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Doi
authors.forename: Shijie
authors.initials: S
authors.lastname: Jin
authors.forename: Endong
authors.initials: E
authors.lastname: Li
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Sonobe
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Takeuchi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mizuno
authors.forename: Akio
authors.initials: A
authors.lastname: Suzumura
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D007378:Interleukins / Q000378:metabolism*; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000502:physiology; D009498:Neurotoxins / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D007378:Interleukins; D009498:Neurotoxins; D016212:Transforming Growth Factor beta; C552364:interleukin-34, mouse