Activated microglia represent a major source of inflammatory factors in Alzheimer's disease and a possible source of cytotoxic factors. β-Amyloid (Aβ) peptide, the predominant component in amyloid plaques, has been shown to activate microglia and stimulate their production of inflammatory factors. The present study was performed to analyze the responses of microglia to different forms of Aβ, with regard to release of the proinflammatory cytokines interleukin-1α (IL-1α), IL-1β, tumor necrosis factor-α (TNF-α), IL-6, and interferon-γ (IFN-γ), as well as the IL-1 receptor antagonist (IL-1ra). Primary cultures of microglia from rat neonatal cerebral cortex were incubated with freshly dissolved Aβ1-40 or Aβ1-42, Aβ1-40 fibrils, Aβ1-40 βamy balls, or vehicle. Aβ1-40 fibrils did not significantly stimulate any of these cytokines. Freshly dissolved Aβ1-40 resulted in a marked increase in the release of IL-1β, and freshly dissolved Aβ1-42 significantly stimulated both IL-1α and IFN-γ secretion. The Aβ1-40 βamy balls stimulated the secretion of IL-1α and IL-1β. Incubation with Aβ peptides did not affect the secretion of IL-1ra, IL-6, or TNF-α. In the case of IL-1β, the response is correlated with the presence of Aβ peptide as monomers and oligomers.
|Number of pages||12|
|Journal||Journal of Molecular Neuroscience|
|State||Published - Sep 2005|
Bibliographical noteFunding Information:
We thank Dr. Stefan Spulber at Karolinska Insti-tutet, Neurotec Department, Division of Experimental Geriatrics, for assistance with the design of the cell counting. We are also grateful to Professor Bengt Winblad (Karolinska Institutet, also of the Division of Experimental Geriatrics) for continuous support and encouragement. This work was supported by grants from the Swedish Research Council (072194), Stiftelsen för Gamla Tjänarinnor, Gun och Bertil Stohnes stiftelse, Insamlingsstiftelsen för Alzheimer-och Demensforskning, Åke Wibergs stiftelse, Alzheimerfonden, Stiftelsen för ålders-forskning, and Magnus Bergvalls Stiftelse. We are also grateful to Bio-Rad (Stockholm, Sweden) for their generous support regarding Luminex assays.
- Alzheimer's disease
- Receptor antagonist
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience