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      Expression of Fractalkine (CX3CL1) and Its Receptor in Endotoxin-Induced Uveitis

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          Abstract

          Background/Aims: Chemokines play a critical role in inflammation and neurodegenerative disease in the central nervous system. In this study, endotoxin-induced uveitis (EIU) was induced to test the expression of fractalkine, a special neuronal chemokine, and its receptor CX3CR1 in acute inflammation of the retina. Methods:EIU was induced by footpad injections of lipopolysaccharide (LPS). Eight rats were sacrificed at each time point (0, 8, 16, 24, 48, and 72 h) after LPS injection. Sections were made for histopathological tests. Immunohistochemistry was performed using antibodies specific to fractalkine and CX3CR1. Retinas were collected, and total protein and mRNA from both the induced and control rats were extracted. mRNA and protein expression of fractalkine and CX3CR1 in the retina were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blots, respectively. Results: The EIU model was successfully induced. In control rats, both fractalkine and its receptor CX3CR1 were detected in the retina. LPS injection induced a transient upregulation of both proteins at 24 h as determined by the increased number of positively stained cells as well as increased levels of mRNA and protein (p < 0.05). Conclusion: A transitory increased expression of fractalkine and its receptor CX3CR1 occurred at the crest time of EIU, and this change in expression may play a role in the turnover of LPS-induced acute retina inflammation.

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          Most cited references15

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          Role of the immune system in chronic pain.

          During the past two decades, an important focus of pain research has been the study of chronic pain mechanisms, particularly the processes that lead to the abnormal sensitivity - spontaneous pain and hyperalgesia - that is associated with these states. For some time it has been recognized that inflammatory mediators released from immune cells can contribute to these persistent pain states. However, it has only recently become clear that immune cell products might have a crucial role not just in inflammatory pain, but also in neuropathic pain caused by damage to peripheral nerves or to the CNS.
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            Microglia as neuroprotective, immunocompetent cells of the CNS.

            The role of glial cells is to support and sustain proper neuronal function and microglia are no exception to this. This viewpoint article emphasizes the fundamental interdependence of microglia and neurons and takes a look at the possibility of what could happen if microglial cells became dysfunctional as a result of aging, genetics, or epigenetics. Could microglial senescence be a factor in the pathogenesis of Alzheimer's and other neurodegenerative diseases? The cautious answer to that question is 'yes'. Future studies along these lines may provide novel insights into microglial involvement in neurodegenerative disease pathogenesis. Copyright 2002 Wiley-Liss, Inc.
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              Production and neuroprotective functions of fractalkine in the central nervous system.

              The CX3C-chemokine, fractalkine is reportedly to be expressed in the central nervous system, and up-regulated in certain pathological conditions, such as HIV encephalopathy and multiple sclerosis. In the present study, we examined the production of fractalkine and the expression of its receptor, CX3CR1 in murine glial and neuronal cell in vitro, and investigated its neuroprotective functions. Both fractalkine and CX3CR1 were expressed constitutively in neurons, microglia, and astrocytes. Neither the production of fractalkine nor its receptor expression was up-regulated by lipopolysaccharide (LPS), as measured by mRNA expression and protein synthesis. Fractalkine dose-dependently suppressed the production of nitric oxide (NO), interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha with activated microglia. It also significantly suppressed neuronal cell death induced by microglia activated with LPS and interferon-gamma, in a dose-dependent manner. These results suggest the possible functions of fractalkine as an intrinsic inhibitor against neurotoxicity by activated microglia.
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                Author and article information

                Journal
                ORE
                Ophthalmic Res
                10.1159/issn.0030-3747
                Ophthalmic Research
                S. Karger AG
                0030-3747
                1423-0259
                2009
                November 2009
                31 July 2009
                : 42
                : 3
                : 160-166
                Affiliations
                Department of Ophthalmology, People’s Hospital, Peking University, Beijing, PR China
                Article
                230878 Ophthalmic Res 2009;42:160–166
                10.1159/000230878
                19648777
                df3c297d-33a7-4fa0-8854-5874253e6a19
                © 2009 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.

                History
                : 18 November 2008
                : 27 February 2009
                Page count
                Figures: 3, Tables: 1, References: 27, Pages: 7
                Categories
                Original Paper

                Vision sciences,Ophthalmology & Optometry,Pathology
                Fractalkine,Chemokine,Endotoxin-induced uveitis,Chemoattractant

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