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Title: Resveratrol modulates cytokine-induced Jak/STAT activation more efficiently than 5-aminosalicylic acid: an in vitro approach
Authors: Serra, Diana 
Rufino, Ana T. 
Mendes, Alexandrina F. 
Almeida, Leonor M. 
Dinis, Teresa C. P. 
Issue Date: 2014
Publisher: Public Library of Science
Project: This work was supported by the grants PTDC/SAU-OSM/102907/2008 and PEst-C/SAU/LA0001/2013-2014, funded by FCT (Portuguese Foundation for Science and Technology) and FEDER/COMPETE (European Fund of Regional Development/Operational Program Factors of Competitiveness). Diana Serra is a recipient of the grant SFRH/BD/7541/2010 from FCT 
Serial title, monograph or event: PLoS ONE
Volume: 9
Issue: 10
Abstract: Background: Many advances have been recently made focused on the valuable help of dietary polyphenols in chronic inflammatory diseases. On the other hand, current treatment options for intestinal bowel disease patients are unsatisfying and, for this reason, it is estimated that many patients use dietary supplements to achieve extra benefits. Aim: The aim of this work was to analyze under a mechanistic perspective the anti-inflammatory potential of resveratrol, a natural polyphenolic compound, and to compare it with a pharmaceutical agent, 5-aminosalicylic acid, using the intestinal HT-29 cell line, as a cellular model. Methodology and Principal Findings: In the present study, HT-29 colon epithelial cells were pre-treated with 25 mM resveratrol and/or 500 mM 5-aminosalicylic acid and then exposed to a combination of cytokines (IL-1a, TNF-a, IFN-c) for a certain period of time. Our data showed that resveratrol, used in a concentration 20 times lower than 5-aminosalicylic acid, was able to significantly reduce NO and PGE2 production, iNOS and COX-2 expression and reactive oxidant species formation induced by the cytokine challenge. However, as already verified with 5-aminosalicylic acid, in spite of not exhibiting any effect on IkB-a degradation, resveratrol down-regulated JAK-STAT pathway, decreasing the levels of activated STAT1 in the nucleus. Additionally, resveratrol decreased the cytokine-stimulated activation of SAPK/JNK pathway but did not counteract the cytokine-triggered negative feedback mechanism of STAT1, through p38 MAPK. Conclusion/Significance: Taken together, our results show that resveratrol may be considered a future nutraceutical approach, promoting remission periods, limiting the inflammatory process and preventing colorectal cancer, which is common in these patients.
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0109048
Rights: openAccess
Appears in Collections:FFUC- Artigos em Revistas Internacionais
I&D CNC - Artigos em Revistas Internacionais

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