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      Human Amylin Stimulates Inflammatory Cytokine Secretion from Human Glioma Cells

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          Abstract

          Chronic neurodegeneration in the brains of Alzheimer’s disease (AD) patients may be mediated, at least in part, by the ability of amyloid beta (Aβ) to exacerbate inflammatory pathways in a conformation-dependent manner. In this regard, we previously reported that the Aβ-peptide-mediated potentiation of inflammatory cytokine secretion from interleukin-1β (IL-1β)-stimulated human astrocytoma cells was conformation dependent. Other amyloidogenic peptides, such as human amylin, which display similar conformation-dependent neurotoxic effects, may also elicit inflammatory cytokine secretion from glial cells. To test this hypothesis, we compared human and rat amylin for the effects on cytokine production in U-373 MG human astrocytoma cells. Human amylin alone stimulated U-373 MG cells to secrete IL-6 and IL-8 in a concentration-dependent manner with maximum effects seen at 10–25 μ M peptide. In addition, human amylin markedly potentiated IL-1β-stimulated cytokine production with a similar concentration dependence. In contrast, nonamyloidogenic rat amylin modestly stimulated cytokine secretion, either alone or combined with IL-1β. Aging human amylin resulted in diminished cytokine secretion, probably due to the formation of large, less active aggregates. In agreement with our previous studies using Aβ, extracellular Ca<sup>2+</sup> was necessary for human amylin stimulation of cytokine secretion. Our data suggest that amyloidogenic peptides promote cytokine secretion through similar β-sheeted secondary-structure- and extracellular-Ca<sup>2+</sup>-dependent mechanisms.

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          Most cited references 11

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          Cell biology of the amyloid beta-protein precursor and the mechanism of Alzheimer's disease.

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            Alzheimer's Disease--Genotypes, Phenotype, and Treatments

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              β-Amyloid precursor protein metabolites and loss of neuronal Ca2+ homeostasis in Alzheimer's disease

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                Author and article information

                Journal
                NIM
                Neuroimmunomodulation
                10.1159/issn.1021-7401
                Neuroimmunomodulation
                S. Karger AG
                1021-7401
                1423-0216
                2000
                April 2000
                05 April 2000
                : 7
                : 3
                : 147-152
                Affiliations
                Neuroscience Diseases Research Division, Lilly Research Laboratories, Eli Lilly and Co., Lilly Corporate Center, <city>Indianapolis, Ind.</city>, USA
                Article
                26432 Neuroimmunomodulation 2000;7:147–152
                10.1159/000026432
                10754402
                © 2000 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 3, References: 49, Pages: 6
                Categories
                Original Paper

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