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Hypersensitive cytokine response to beta-amyloid 25-35 in astroglial cells from IL-1 receptor type I-deficient mice.

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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.
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Document Type: Research Article

Affiliations: Department of Neurochemistry and Neurotoxicology, The Arrhenius Laboratories for Natural Sciences, Stockholm University, S-106 91 Stockholm, Sweden.

Publication date: January 1, 1998

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  • The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.

    The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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