Franziska Bollmann, Julia Art, Jenny Henke, Katharina Schrick, Verena Besche, Matthias Bros, Huige Li, Daniel Siuda, Norbert Handler, Florian Bauer, Thomas Erker, Felix Behnke, Bettina Mönch, Lorena Härdle, Markus Hoffmann, Ching-Yi Chen, Ulrich Förstermann, Verena M. Dirsch, Oliver Werz, Hartmut Kleinert, Andrea Pautz
- Resveratrol shows beneficial effects in inflammation-based diseases like cancer, cardiovascular and chronic inflammatory diseases. Therefore, the molecular mechanisms of the anti-inflammatory resveratrol effects deserve more attention. In human epithelial DLD-1 and monocytic Mono Mac 6 cells resveratrol decreased the expression of iNOS, IL-8 and TNF-α by reducing mRNA stability without inhibition of the promoter activity. Shown by pharmacological and siRNA-mediated inhibition, the observed effects are SIRT1-independent. Target-fishing and drug responsive target stability experiments showed selective binding of resveratrol to the RNA-binding protein KSRP, a central post-transcriptional regulator of pro-inflammatory gene expression. Knockdown of KSRP expression prevented resveratrol-induced mRNA destabilization in human and murine cells. Resveratrol did not change KSRP expression, but immunoprecipitation experiments indicated that resveratrol reduces the p38 MAPK-related inhibitory KSRP threonine phosphorylation, without blocking p38 MAPK activation or activity. Mutation of the p38 MAPK target site in KSRP blocked the resveratrol effect on pro-inflammatory gene expression. In addition, resveratrol incubation enhanced KSRP-exosome interaction, which is important for mRNA degradation. Finally, resveratrol incubation enhanced its intra-cellular binding to the IL-8, iNOS and TNF-α mRNA. Therefore, modulation of KSRP mRNA binding activity and, thereby, enhancement of mRNA degradation seems to be the common denominator of many anti-inflammatory effects of resveratrol.
MetadatenAuthor: | Franziska BollmannGND, Julia Art, Jenny Henke, Katharina Schrick, Verena Besche, Matthias Bros, Huige Li, Daniel Siuda, Norbert Handler, Florian Bauer, Thomas Erker, Felix Behnke, Bettina Mönch, Lorena HärdleGND, Markus Hoffmann, Ching-Yi Chen, Ulrich FörstermannGND, Verena M. Dirsch, Oliver WerzORCiDGND, Hartmut Kleinert, Andrea PautzORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-373267 |
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DOI: | https://doi.org/10.1093/nar/gku1033 |
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ISSN: | 1362-4962 |
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ISSN: | 0305-1048 |
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Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/25352548 |
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Parent Title (English): | Nucleic acids research |
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Publisher: | Oxford Univ. Press |
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Place of publication: | Oxford |
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Document Type: | Article |
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Language: | English |
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Date of Publication (online): | 2014/10/28 |
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Date of first Publication: | 2014/10/28 |
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Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Release Date: | 2015/04/29 |
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Volume: | 42 |
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Issue: | 20 |
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Page Number: | 15 |
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First Page: | 12555 |
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Last Page: | 12569 |
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Note: | © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
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HeBIS-PPN: | 369111699 |
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Institutes: | Medizin / Medizin |
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| Fachübergreifende Einrichtungen / Zentrum für Arzneimittelforschung, Entwicklung und Sicherheit (ZAFES) |
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Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Sammlungen: | Universitätspublikationen |
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Licence (German): | Creative Commons - Namensnennung-Nicht kommerziell - Keine Bearbeitung 4.0 |
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