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      Interleukin-6 Stimulates Tubular Regeneration in Rats with Glycerol-Induced Acute Renal Failure

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          Abstract

          Interleukin-6 stimulates tubular regeneration in rats with glycerol-induced acute renal failure. Background: Interleukin 6 (IL-6) is a pleiotropic cytokine released after endotoxemia, trauma and organ injury. IL-6 may act in cellular proliferation activating transduction signals and Ras/Map cascade or the HGF/c-met axis. We tested the effect of IL-6 in the regeneration of tubular epithelia after acute tubular necrosis (ATN) in rats. Methods: Rats with glycerol-induced acute renal failure (Gly-ARF) were treated with IL-6 200 µg/kg/day. Functional, histological and immunohistochemical tests were done 24 and 72 h after Gly-ARF to localise mitotic cells (BrdU). The renal expression of c-met (Western-Blot) and circulating levels of HGF (ELISA) were also determined. Results: Rats with Gly-ARF had reduced creatinine clearance that was not influenced by IL-6. The histological appearance of ATN was also unaffected by IL-6. The IL-6 treated rats showed a significant increase in tubular cell proliferation in cortex and medulla, as well as in the expression of c-met protein in the renal cortex, compared to untreated Gly-ARF rats. The plasma HGF concentration was equally elevated in treated and untreated Gly-ARF rats. Discussion: IL-6 stimulates tubular regeneration after Gly-ARF and increases the expression of c-met in the renal cortex. Gly-ARF rats have high circulating levels of HGF that is targeted to act in the injured kidneys by the IL-6 overexpressed renal c-met.

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          Cadmium-induced renal damage and proinflammatory cytokines: possible role of IL-6 in tubular epithelial cell regeneration.

          Cadmium exposure in humans and experimental animals produces renal damage characterized by degeneration and necrosis of tubular epithelial cells followed by interstitial inflammation and eventual regeneration of proximal tubular cells. Since chronic kidney diseases are often associated with the presence of inflammatory cytokines and cadmium has been reported to alter cytokine expression in monocytes and the Kupffer cells of the liver, we investigated the role of proinflammatory cytokines in cadmium-induced nephrotoxicity. Increases in TNF-alpha and IL-6 cytokine mRNA transcripts and secretion were observed in the kidney following exposure of LPS-primed mice to a total of 21 mg/kg body weight cadmium administered over a 14-week period. IL-6 was the predominant cytokine expressed and was found to be present in mesangial cells. Cadmium, in the presence of LPS, was able to induce IL-6 secretion in vitro from mouse glomerular mesangial cells. Proliferative cell nuclear antigen (PCNA) staining revealed increases in regeneration of tubular epithelial cells following cadmium exposure. Furthermore, renal tubular epithelial cells responded to IL-6 by marked proliferation. Taken together, these data suggest that cadmium-induced IL-6 secretion in the kidney may act to support the regeneration of renal tubular epithelial cells that occurs in the course of cadmium nephrotoxicity.
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            C-met protooncogene expression and its regulation by cytokines in the regenerating pancreas and in pancreatic cancer cells.

            Activation of the receptor c-met stimulates motility, mitosis, morphogenesis, processes involved in organ regeneration, or progression of malignancies. In the present study we investigated the expression of c-met protein in the regenerating pancreas and characterized the influence of cytokines on c-met expression.
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              Interleukin-6 induces proliferation of rat hepatocytes in vivo

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                Author and article information

                Journal
                NEF
                Nephron
                10.1159/issn.1660-8151
                Nephron
                S. Karger AG
                1660-8151
                2235-3186
                2002
                September 2002
                14 August 2002
                : 92
                : 1
                : 192-199
                Affiliations
                Division of Nephrology, Faculty of Medical Sciences, State University of Campinas, Campinas, São Paulo, Brasil
                Article
                64478 Nephron 2002;92:192–199
                10.1159/000064478
                12187102
                65bad185-ff08-43a0-8170-f33da55a6d8d
                © 2002 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
                : 07 November 2001
                Page count
                Figures: 4, Tables: 2, References: 40, Pages: 8
                Categories
                Original Paper

                Cardiovascular Medicine,Nephrology
                Interleukin-6,Acute renal failure,Tubular regeneration,HGF/c-met axis

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