beta-Amyloid induces increased release of interleukin-1 beta from lipopolysaccharide-activated human monocytes.
Previous reports have demonstrated that IL-1 is elevated in the Alzheimer's disease brain. We propose that beta-amyloid (A beta) in senile plaques triggers microglial interleukin-1(IL-1) release. Since microglia and monocytes have similar lineage and functions, the human monocyte cell line, THP-1, was used to determine whether A beta peptides can stimulate release of IL-1 beta. THP-1 cells were grown in culture with LPS and incubated with various A beta peptides (0.5-10 microM). IL-1 released into the medium was measured using either an IL-1 beta ELISA or an IL-1 bioassay. Treatment of activated THP-1 cells with A beta 25-35, fibrillar A beta 1-40, or A beta 1-42 significantly elevated IL-1 beta release. A beta 25-35 with a scrambled sequence or non-fibrillar A beta 1-40 did not significantly change IL-1 beta release from activated THP-1 cells. The A beta 25-35- and fibrillar A beta 1-40 induced IL-1 beta release was dose-dependent. IL-1 released following treatment with A beta 25-35 and measured using an IL-1 bioassay gave similar results. The present report provides evidence that A beta is capable of elevating release of functional IL-1 beta, a potent pro-inflammatory cytokine, from macrophages/microglia and provides support that a chronic local inflammatory response is an ongoing phenomenon within and surrounding senile plaques.
Lorton
D
D
Gliatech Inc., Beachwood, OH 44122-5813, USA.
Kocsis
J M
JM
King
L
L
Madden
K
K
Brunden
K R
KR
D000544:Alzheimer Disease / Q000276:immunology / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D008070:Lipopolysaccharides; D017628:Microglia / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D007375:Interleukin-1; D008070:Lipopolysaccharides; D010446:Peptide Fragments