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      Interferon β Affects Retinal Pigment Epithelial Cell Proliferation via Protein Kinase C Pathways

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          Abstract

          Background: The aim of this study is to see the effect of interferon β (IFN-β) on cell proliferation and the protein kinase C (PKC) signaling pathway. Methods: Proliferation of cultured human retinal pigment epithelium (RPE) cells, with various concentrations of IFN-β, and with or without 3% fetal calf serum (FCS), was assessed by cell counting. Effects of short (3 h) or prolonged (48 h) exposure of RPE cells to natural human IFN-β were assessed by <sup>3</sup>H-thymidine uptake. Cytosolic and membranous PKC activity over time in cells treated with IFN-β and calphostin C was also measured. Results: IFN-β inhibited the increased proliferation by FCS in the prolonged-exposure assay. The PKC inhibitor calphostin C also showed an inhibitory effect on RPE cell growth and <sup>3</sup>H-thymidine uptake in the chronic exposure with FCS. Short treatment with IFN-β had no inhibitory or stimulatory effect on <sup>3</sup>H-thymidine uptake. Cytosolic and membranous PKC activity was strongly upregulated after short IFN-β exposure but returned to original levels after 1 h. PKC activity was downregulated both in the cytosol and membrane after 24 or 48 h. Conclusion: IFN-β inhibited RPE proliferation in vitro and the effect is mediated by upregulation of the PKC pathway.

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          Most cited references 3

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          The molecular heterogeneity of protein kinase C and its implications for cellular regulation.

           Y Nishizuka (1988)
          Protein kinase C is now known to be a large family of proteins, with multiple subspecies that have subtle individual enzymological characteristics. Some members of the family exhibit distinct patterns of tissue expression and intracellular localization; different kinases probably have distinct functions in the processing and modulation of a variety of physiological and pathological responses to external signals.
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            Involvement of the protein kinase pathway in melanin synthesis by chick retinal pigment epithelial cells.

            Protein kinases are involved in a variety of cellular functions and cell proliferation in eyes. We have explored the involvement of protein kinase C (PKC) in cell proliferation and melanin synthesis by chick retinal pigment epithelial (RPE) cells in vitro. This was achieved by incubation of confluent RPE cells with known inhibitors of protein kinase, H-7, W-7, H-8, and staurosporine. Chick RPE cells were cultured in the presence or absence of the protein kinase inhibitors for a 10-day period. Effects of the inhibitors on cell proliferation and melanin synthesis, as an indication of cell differentiation, were assessed by counting the number of surviving cells and by measuring the melanin content in the cells, respectively. H-7, W-7, and staurosporine inhibited cell proliferation and increased melanin synthesis in a concentration-dependent manner during culture; however, H-8 did not produce these cellular effects. These findings indicate that PKC and calcium/calmodulin-dependent kinase pathways are involved in the proliferation and differentiation of chick RPE cells. Copyright 2000 Academic Press.
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              Subretinal Neovascularization in the Rat Induced by IRBP Synthetic Peptides

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                Author and article information

                Journal
                OPH
                Ophthalmologica
                10.1159/issn.0030-3755
                Ophthalmologica
                S. Karger AG
                0030-3755
                1423-0267
                2001
                December 2001
                30 November 2001
                : 215
                : 6
                : 401-407
                Affiliations
                aDepartment of Ophthalmology, Faculty of Medicine, Kyushu University, Fukuoka, Japan; bDoheny Eye Institute and Departments of Ophthalmology, cPathology and dCell and Neurobiology, University of Southern California School of Medicine, Los Angeles, Calif., USA
                Article
                50897 Ophthalmologica 2001;215:401–407
                10.1159/000050897
                11741104
                © 2001 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: 4, Tables: 1, References: 20, Pages: 7
                Categories
                Original Paper · Travail original · Originalarbeit

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