Amyloid β oligomers induce interleukin-1β production in primary microglia in a cathepsin B- and reactive oxygen species-dependent manner.

• Taneo, Jun

• Adachi, Takumi

• Yoshida, Aiko

• Takayasu, Kunio

• Takahara, Kazuhiko

• Inaba, Kayo

Abstract

Amyloid β (Aβ) peptide, a causative agent of Alzheimer's disease, forms two types of aggregates: oligomers and fibrils. These aggregates induce inflammatory responses, such as interleukin-1β (IL-1β) production by microglia, which are macrophage-like cells located in the brain. In this study, we examined the effect of the two forms of Aβ aggregates on IL-1β production in mouse primary microglia. We prepared Aβ oligomer and fibril from Aβ (1-42) peptide invitro. We analyzed the characteristics of these oligomers and fibrils by electrophoresis and atomic force microscopy. Interestingly, Aβ oligomers but not Aβ monomers or fibrils induced robust IL-1β production in the presence of lipopolysaccharide. Moreover, Aβ oligomers induced endo/phagolysosome rupture, which released cathepsin B into the cytoplasm. Aβ oligomer-induced IL-1β production was inhibited not only by the cathepsin B inhibitor CA-074-Me but also by the reactive oxygen species (ROS) inhibitor N-acetylcysteine. Random chemical crosslinking abolished the ability of the oligomers to induce IL-1β. Thus, multimerization and fibrillization causes Aβ oligomers to lose the ability to induce IL-1β. These results indicate that Aβ oligomers, but not fibrils, induce IL-1β production in primary microglia in a cathepsin B- and ROS-dependent manner.

Journal

• Biochemical and biophysical research communications

  Biochemical and biophysical research communications 458 (3), 561-567, 2015-03-13

  Elsevier Inc.

Keywords

• AFM
• Amyloid β
• Fibrils
• IL-1β
• Microglia
• Oligomers

Details

• CRID: 1050282810787368448
• NII Article ID: 120005575184
• NII Book ID: AA00564395
• ISSN: 0006291X
• HANDLE: 2433/196665
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • CiNii Articles