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Knockout of the c-Jun N-terminal Kinase 2 aggravates the development of mild chronic dextran sulfate sodium colitis independently of expression of intestinal cytokines TNFα, TGFB1, and IL-6
INTRODUCTION: The c-Jun N-terminal kinases (JNKs) are involved in signal transduction of inflammatory bowel diseases. The aim of this study was to examine the function of JNKs by using a low-dose dextran sulfate sodium (DSS) model in JNK1 knockout mice (Mapk8−/−), JNK2 knockout mice (Mapk9−/−), and...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3576002/ https://www.ncbi.nlm.nih.gov/pubmed/23426157 http://dx.doi.org/10.2147/JIR.S36415 |
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author | Kersting, Sabine Reinecke, Kirstin Hilgert, Christoph Janot, Monika S Haarmann, Elisabeth Albrecht, Martin Müller, Annette M Herdegen, Thomas Mittelkötter, Ulrich Uhl, Waldemar Chromik, Ansgar M |
author_facet | Kersting, Sabine Reinecke, Kirstin Hilgert, Christoph Janot, Monika S Haarmann, Elisabeth Albrecht, Martin Müller, Annette M Herdegen, Thomas Mittelkötter, Ulrich Uhl, Waldemar Chromik, Ansgar M |
author_sort | Kersting, Sabine |
collection | PubMed |
description | INTRODUCTION: The c-Jun N-terminal kinases (JNKs) are involved in signal transduction of inflammatory bowel diseases. The aim of this study was to examine the function of JNKs by using a low-dose dextran sulfate sodium (DSS) model in JNK1 knockout mice (Mapk8−/−), JNK2 knockout mice (Mapk9−/−), and wild-type controls (WT1, WT2). METHODS: The animals were evaluated daily using a disease activity index. After 30 days, the intestine was evaluated histologically with a crypt damage score. CD4+ and CD8+ cells were quantified using immunofluorescence. Analysis of tumor necrosis factor-α (TNFα), interleukin-6 (IL-6), and transforming growth factor β1 (TGFB1) expression was carried out using LightCycler(®) real-time polymerase chain reaction. RESULTS: Cyclic administration of low-dose DSS (1%) was not able to induce features of chronic colitis in Mapk8−/− WT2 mice. By contrast, DSS administration significantly increased the disease activity index in WT1 and Mapk9−/− mice. In Mapk9−/− mice, the crypt damage score and the number of CD4+ and CD8+ cells as features of chronic colitis/inflammation were also significantly elevated. Expression of TNFα, IL-6, and TGFB1 was not altered by the JNK knockout. CONCLUSION: Administering DSS at a defined low concentration that is unable to induce colitis in WT animals leads to clinically and histologically detectable chronic colitis in Mapk9−/− mice. The reason for this disease-inducing effect resulting from the loss of JNK2 remains to be elucidated. Expression of TNFα, IL-6, and TGFB1 does not appear to be involved; proapoptotic JNK2 may prolong the activity of proinflammatory immune cells, leading to perpetuation of the inflammation. |
format | Online Article Text |
id | pubmed-3576002 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-35760022013-02-20 Knockout of the c-Jun N-terminal Kinase 2 aggravates the development of mild chronic dextran sulfate sodium colitis independently of expression of intestinal cytokines TNFα, TGFB1, and IL-6 Kersting, Sabine Reinecke, Kirstin Hilgert, Christoph Janot, Monika S Haarmann, Elisabeth Albrecht, Martin Müller, Annette M Herdegen, Thomas Mittelkötter, Ulrich Uhl, Waldemar Chromik, Ansgar M J Inflamm Res Original Research INTRODUCTION: The c-Jun N-terminal kinases (JNKs) are involved in signal transduction of inflammatory bowel diseases. The aim of this study was to examine the function of JNKs by using a low-dose dextran sulfate sodium (DSS) model in JNK1 knockout mice (Mapk8−/−), JNK2 knockout mice (Mapk9−/−), and wild-type controls (WT1, WT2). METHODS: The animals were evaluated daily using a disease activity index. After 30 days, the intestine was evaluated histologically with a crypt damage score. CD4+ and CD8+ cells were quantified using immunofluorescence. Analysis of tumor necrosis factor-α (TNFα), interleukin-6 (IL-6), and transforming growth factor β1 (TGFB1) expression was carried out using LightCycler(®) real-time polymerase chain reaction. RESULTS: Cyclic administration of low-dose DSS (1%) was not able to induce features of chronic colitis in Mapk8−/− WT2 mice. By contrast, DSS administration significantly increased the disease activity index in WT1 and Mapk9−/− mice. In Mapk9−/− mice, the crypt damage score and the number of CD4+ and CD8+ cells as features of chronic colitis/inflammation were also significantly elevated. Expression of TNFα, IL-6, and TGFB1 was not altered by the JNK knockout. CONCLUSION: Administering DSS at a defined low concentration that is unable to induce colitis in WT animals leads to clinically and histologically detectable chronic colitis in Mapk9−/− mice. The reason for this disease-inducing effect resulting from the loss of JNK2 remains to be elucidated. Expression of TNFα, IL-6, and TGFB1 does not appear to be involved; proapoptotic JNK2 may prolong the activity of proinflammatory immune cells, leading to perpetuation of the inflammation. Dove Medical Press 2013-02-12 /pmc/articles/PMC3576002/ /pubmed/23426157 http://dx.doi.org/10.2147/JIR.S36415 Text en © 2013 Kersting et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited. |
spellingShingle | Original Research Kersting, Sabine Reinecke, Kirstin Hilgert, Christoph Janot, Monika S Haarmann, Elisabeth Albrecht, Martin Müller, Annette M Herdegen, Thomas Mittelkötter, Ulrich Uhl, Waldemar Chromik, Ansgar M Knockout of the c-Jun N-terminal Kinase 2 aggravates the development of mild chronic dextran sulfate sodium colitis independently of expression of intestinal cytokines TNFα, TGFB1, and IL-6 |
title | Knockout of the c-Jun N-terminal Kinase 2 aggravates the development of mild chronic dextran sulfate sodium colitis independently of expression of intestinal cytokines TNFα, TGFB1, and IL-6 |
title_full | Knockout of the c-Jun N-terminal Kinase 2 aggravates the development of mild chronic dextran sulfate sodium colitis independently of expression of intestinal cytokines TNFα, TGFB1, and IL-6 |
title_fullStr | Knockout of the c-Jun N-terminal Kinase 2 aggravates the development of mild chronic dextran sulfate sodium colitis independently of expression of intestinal cytokines TNFα, TGFB1, and IL-6 |
title_full_unstemmed | Knockout of the c-Jun N-terminal Kinase 2 aggravates the development of mild chronic dextran sulfate sodium colitis independently of expression of intestinal cytokines TNFα, TGFB1, and IL-6 |
title_short | Knockout of the c-Jun N-terminal Kinase 2 aggravates the development of mild chronic dextran sulfate sodium colitis independently of expression of intestinal cytokines TNFα, TGFB1, and IL-6 |
title_sort | knockout of the c-jun n-terminal kinase 2 aggravates the development of mild chronic dextran sulfate sodium colitis independently of expression of intestinal cytokines tnfα, tgfb1, and il-6 |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3576002/ https://www.ncbi.nlm.nih.gov/pubmed/23426157 http://dx.doi.org/10.2147/JIR.S36415 |
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