Hypersensitive cytokine response to beta-amyloid 25-35 in astroglial cells from IL-1 receptor type I-deficient mice.
betaA25-35, a neurotoxic fragment of the Alzheimer beta-amyloid peptide (betaA), acts as a strong inducer of pro-inflammatory cytokines, such as interleukin (IL)-1 and IL-6, in glial cells. Since IL-1 is known to induce expression of both IL-1 and IL-6, we have investigated to what extent the induction of IL-1alpha and IL-6 by betaA25-35, is dependent on the IL-1 receptor type I (IL-1RI), the only known signalling IL-1 receptor. Primary astroglial cell cultures prepared from wild-type and IL-1RI-deficient mice were incubated in the presence of betaA25-35 (100 microM) for 19 h, followed by analysis of mRNA levels of IL-1alpha and IL-6. Cell cultures treated with betaA25-35 showed a significant increase in mRNA levels for IL-1alpha and IL-6 and in addition increased levels of IL-1alpha immunoreactivity. A supersensitive IL-1alpha response was observed in astroglial cell cultures lacking the IL-1 RI as compared to betaA25-35 treated cell cultures from wild-type mice. In contrast the betaA25-35-induced increase of IL-6 was lower in the absence of IL-1RI. In conclusion, these results suggest that a functional IL-1 signal transduction is not necessary for induction of mRNA levels of IL-1alpha and IL-6 in astroglial cell cultures treated with betaA25-35, but that induction of IL-6 involves at least two distinct mechanisms, one of which occurs via activation of the IL-1RI.
Eriksson
G
G
Department of Neurochemistry and Neurotoxicology, The Arrhenius Laboratories for Natural Sciences, Stockholm University, S-106 91 Stockholm, Sweden.
Zetterström
M
M
Cortes Toro
V
V
Bartfai
T
T
Iverfeldt
K
K
D016229:Amyloid beta-Peptides / Q000276:immunology* / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D007375:Interleukin-1 / Q000235:genetics / Q000276:immunology*; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D010446:Peptide Fragments / Q000276:immunology* / Q000494:pharmacology; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology*
D016229:Amyloid beta-Peptides; D007375:Interleukin-1; D015850:Interleukin-6; D010446:Peptide Fragments; D017472:Receptors, Interleukin-1; D014409:Tumor Necrosis Factor-alpha; C074636:amyloid beta-protein (25-35)