Beta-amyloid fragment potentiates IL-6 and TNF-alpha secretion by LPS in astrocytes but not in microglia.
The effect of a peptide homologous to the biologically active fragment of beta amyloid 25-35 (beta 25-35) was studied on interleukin 6 (IL-6) and tumour necrosis factor (TNF-alpha) secretion induced by lipopolysaccharide (LPS) in primary rat astrocytes and microglia. Twenty-four hour exposure to LPS (50 ng/ml) induced IL-6 and TNF-alpha both in astrocytes and in microglial cells, while the effect of beta 25-35 (50 microM) per se was negligible in both cell types. In microglial cells, the application of beta peptide did not alter the production of either cytokine induced by LPS. However, beta 25-35 strongly amplified the production of both IL-6 and TNF-alpha in astrocytes. These findings confirm the complex interaction between cytokines and amyloidogenesis in Alzheimer's disease and indicate that astrocytes rather than microglia respond to the beta amyloid fragment, suggesting that these cells may be actively involved in cytokine-mediated events in AD.
Forloni
G
G
Biology of Neurodegenerative Disorders Laboratory, Istituto di Ricerche Farmacologiche "Mario Negri", via Eritrea 62, Milano, 20157, Italy.
Mangiarotti
F
F
Angeretti
N
N
Lucca
E
E
De Simoni
M G
MG
D016229:Amyloid beta-Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D000963:Antimetabolites / Q000138:chemical synthesis / Q000494:pharmacology*; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D000963:Antimetabolites; D015850:Interleukin-6; D008070:Lipopolysaccharides; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; C074636:amyloid beta-protein (25-35)