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Activation of counter-regulatory mechanisms in a rat renal acute rejection model

BACKGROUND: Microarray analysis provides a powerful approach to identify gene expression alterations following transplantation. In patients the heterogeneity of graft specimens, co-morbidity, co-medications and the challenges in sample collection and preparation complicate conclusions regarding the...

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Autores principales: Edemir, Bayram, Kurian, Sunil M, Eisenacher, Martin, Lang, Detlef, Müller-Tidow, Carsten, Gabriëls, Gert, Salomon, Daniel R, Schlatter, Eberhard
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2262896/
https://www.ncbi.nlm.nih.gov/pubmed/18261221
http://dx.doi.org/10.1186/1471-2164-9-71
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author Edemir, Bayram
Kurian, Sunil M
Eisenacher, Martin
Lang, Detlef
Müller-Tidow, Carsten
Gabriëls, Gert
Salomon, Daniel R
Schlatter, Eberhard
author_facet Edemir, Bayram
Kurian, Sunil M
Eisenacher, Martin
Lang, Detlef
Müller-Tidow, Carsten
Gabriëls, Gert
Salomon, Daniel R
Schlatter, Eberhard
author_sort Edemir, Bayram
collection PubMed
description BACKGROUND: Microarray analysis provides a powerful approach to identify gene expression alterations following transplantation. In patients the heterogeneity of graft specimens, co-morbidity, co-medications and the challenges in sample collection and preparation complicate conclusions regarding the underlying mechanisms of graft injury, rejection and immune regulation. RESULTS: We used a rat kidney transplantation model with strict transplant and sample preparation procedures to analyze genome wide changes in gene expression four days after syngeneic and allogeneic transplantation. Both interventions were associated with substantial changes in gene expression. After allogeneic transplantation, genes and pathways related to transport and metabolism were predominantly down-regulated consistent with rejection-mediated graft injury and dysfunction. Up-regulated genes were primarily related to the acute immune response including antigen presentation, T-cell receptor signaling, apoptosis, interferon signaling and complement cascades. We observed a cytokine and chemokine expression profile consistent with activation of a Th1-cell response. A novel finding was up-regulation of several regulatory and protective genes after allogeneic transplantation, specifically IL10, Bcl2a1, C4bpa, Ctla4, HO-1 and the SOCS family. CONCLUSION: Our data indicate that in parallel with the predicted activation of immune response and tissue injury pathways, there is simultaneous activation of pathways for counter regulatory and protective mechanisms that would balance and limit the ongoing inflammatory/immune responses. The pathophysiological mechanisms behind and the clinical consequences of alterations in expression of these gene classes in acute rejection, injury and dysfunction vs. protection and immunoregulation, prompt further analyses and open new aspects for therapeutic approaches.
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spelling pubmed-22628962008-03-05 Activation of counter-regulatory mechanisms in a rat renal acute rejection model Edemir, Bayram Kurian, Sunil M Eisenacher, Martin Lang, Detlef Müller-Tidow, Carsten Gabriëls, Gert Salomon, Daniel R Schlatter, Eberhard BMC Genomics Research Article BACKGROUND: Microarray analysis provides a powerful approach to identify gene expression alterations following transplantation. In patients the heterogeneity of graft specimens, co-morbidity, co-medications and the challenges in sample collection and preparation complicate conclusions regarding the underlying mechanisms of graft injury, rejection and immune regulation. RESULTS: We used a rat kidney transplantation model with strict transplant and sample preparation procedures to analyze genome wide changes in gene expression four days after syngeneic and allogeneic transplantation. Both interventions were associated with substantial changes in gene expression. After allogeneic transplantation, genes and pathways related to transport and metabolism were predominantly down-regulated consistent with rejection-mediated graft injury and dysfunction. Up-regulated genes were primarily related to the acute immune response including antigen presentation, T-cell receptor signaling, apoptosis, interferon signaling and complement cascades. We observed a cytokine and chemokine expression profile consistent with activation of a Th1-cell response. A novel finding was up-regulation of several regulatory and protective genes after allogeneic transplantation, specifically IL10, Bcl2a1, C4bpa, Ctla4, HO-1 and the SOCS family. CONCLUSION: Our data indicate that in parallel with the predicted activation of immune response and tissue injury pathways, there is simultaneous activation of pathways for counter regulatory and protective mechanisms that would balance and limit the ongoing inflammatory/immune responses. The pathophysiological mechanisms behind and the clinical consequences of alterations in expression of these gene classes in acute rejection, injury and dysfunction vs. protection and immunoregulation, prompt further analyses and open new aspects for therapeutic approaches. BioMed Central 2008-02-08 /pmc/articles/PMC2262896/ /pubmed/18261221 http://dx.doi.org/10.1186/1471-2164-9-71 Text en Copyright © 2008 Edemir et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Edemir, Bayram
Kurian, Sunil M
Eisenacher, Martin
Lang, Detlef
Müller-Tidow, Carsten
Gabriëls, Gert
Salomon, Daniel R
Schlatter, Eberhard
Activation of counter-regulatory mechanisms in a rat renal acute rejection model
title Activation of counter-regulatory mechanisms in a rat renal acute rejection model
title_full Activation of counter-regulatory mechanisms in a rat renal acute rejection model
title_fullStr Activation of counter-regulatory mechanisms in a rat renal acute rejection model
title_full_unstemmed Activation of counter-regulatory mechanisms in a rat renal acute rejection model
title_short Activation of counter-regulatory mechanisms in a rat renal acute rejection model
title_sort activation of counter-regulatory mechanisms in a rat renal acute rejection model
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2262896/
https://www.ncbi.nlm.nih.gov/pubmed/18261221
http://dx.doi.org/10.1186/1471-2164-9-71
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