Beta-amyloid protein structure determines the nature of cytokine release from rat microglia.
Activated microglia represent a major source of inflammatory factors in Alzheimer's disease and a possible source of cytotoxic factors. beta-Amyloid (Abeta) 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 Abeta, with regard to release of the proinflammatory cytokines interleukin-1alpha (IL-1alpha), IL-1beta, tumor necrosis factor-alpha (TNF-alpha), IL-6, and interferon-gamma (IFN-gamma), as well as the IL-1 receptor antagonist (IL-1ra). Primary cultures of microglia from rat neonatal cerebral cortex were incubated with freshly dissolved Abeta1-40 or Abeta1-42, Abeta1-40 fibrils, Abeta1-40 betaamy balls, or vehicle. Abeta1-40 fibrils did not significantly stimulate any of these cytokines. Freshly dissolved Abeta1-40 resulted in a marked increase in the release of IL-1beta, and freshly dissolved Abeta1-42 significantly stimulated both IL-1alpha and IFN-gamma secretion. The Abeta1-40 betaamy balls stimulated the secretion of IL-1alpha and IL-1beta. Incubation with Abeta peptides did not affect the secretion of IL-1ra, IL-6, or TNF-alpha. In the case of IL-1beta, the response is correlated with the presence of Abeta peptide as monomers and oligomers.
Lindberg
Catharina
C
Neurotec Department, Division of Experimental Geriatrics, Karolinska Institutet, Novum, SE-141 86 Stockholm, Sweden. catharina.lindberg@neurotec.ki.se
Selenica
Maj-Linda Bardyl
ML
Westlind-Danielsson
Anita
A
Schultzberg
Marianne
M
D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006801:Humans; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D011247:Pregnancy; D011487:Protein Conformation; D051381:Rats; D017208:Rats, Wistar
D016229:Amyloid beta-Peptides; D016207:Cytokines; D010446:Peptide Fragments