TY  - JOUR
A1  - Bollmann, Franziska
A1  - Art, Julia
A1  - Henke, Jenny
A1  - Schrick, Katharina
A1  - Besche, Verena
A1  - Bros, Matthias
A1  - Li, Huige
A1  - Siuda, Daniel
A1  - Handler, Norbert
A1  - Bauer, Florian
A1  - Erker, Thomas
A1  - Behnke, Felix
A1  - Mönch, Bettina
A1  - Härdle, Lorena
A1  - Hoffmann, Markus
A1  - Chen, Ching-Yi
A1  - Förstermann, Ulrich
A1  - Dirsch, Verena M.
A1  - Werz, Oliver
A1  - Kleinert, Hartmut
A1  - Pautz, Andrea
T1  - Resveratrol post-transcriptionally regulates pro-inflammatory gene expression via regulation of KSRP RNA binding activity
T2  - Nucleic acids research
N2  - 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.
Y1  - 2014
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/37326
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-373267
SN  - 1362-4962
SN  - 0305-1048
N1  - © 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.
VL  - 42
IS  - 20
SP  - 12555
EP  - 12569
PB  - Oxford Univ. Press
CY  - Oxford
ER  -