Resveratrol decreases the expression of genes involved in inflammation through transcriptional regulation

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dc.contributor.authorPinheiro, Daniele Maria Lopes
dc.contributor.authorOliveira, Ana Helena Sales de
dc.contributor.authorCoutinho, Leonam Gomes
dc.contributor.authorFontes, Fabrícia Lima
dc.contributor.authorOliveira, Rayssa Karla de Medeiros
dc.contributor.authorOliveira, Thais Teixeira
dc.contributor.authorFaustino, André Luís Fonseca
dc.contributor.authorSilva, Vandeclécio Lira da
dc.contributor.authorCampos, Julliane Tamara Araújo de Melo
dc.contributor.authorLajus, Tirzah Braz Petta
dc.contributor.authorSouza, Sandro José de
dc.contributor.authorAgnez-Lima, Lucymara Fassarella
dc.date.accessioned2019-01-09T13:14:49Z
dc.date.issued2018-10-24
dc.description.embargo2020-01-01
dc.description.resumoOxidative stress generated during inflammation is associated with a wide range of pathologies. Resveratrol (RESV) displays anti-inflammatory and antioxidant activities, being a candidate for the development of adjuvant therapies for several inflammatory diseases. Despite this potential, the cellular responses induced by RESV are not well known. In this work, transcriptomic analysis was performed following lipopolysaccharide (LPS) stimulation of monocyte cultures in the presence of RESV. Induction of an inflammatory response was observed after LPS treatment and the addition of RESV led to decreases in expression of the inflammatory mediators, tumor necrosis factor-alpha (TNF-α), interleukin-8 (IL-8), and monocyte chemoattractant protein-1 (MCP-1), without cytotoxicity. RNA sequencing revealed 823 upregulated and 2098 downregulated genes (cutoff ≥2.0 or ≤−2.0) after RESV treatment. Gene ontology analysis showed that the upregulated genes were associated with metabolic processes and the cell cycle, consistent with normal cell growth and differentiation under an inflammatory stimulus. The downregulated genes were associated with inflammatory responses, gene expression, and protein modification. The prediction of master regulators using the iRegulon tool showed nuclear respiratory factor 1 (NRF1) and GA-binding protein alpha subunit (GABPA) as the main regulators of the downregulated genes. Using immunoprecipitation and protein expression assays, we observed that RESV was able to decrease protein acetylation patterns, such as acetylated apurinic/apyrimidinic endonuclease-1/reduction-oxidation factor 1 (APE1/Ref-1), and increase histone methylation. In addition, reductions in p65 (nuclear factor-kappa B (NF-κB) subunit) and lysine-specific histone demethylase-1 (LSD1) expression were observed. In conclusion, our data indicate that treatment with RESV caused significant changes in protein acetylation and methylation patterns, suggesting the induction of deacetylase and reduction of demethylase activities that mainly affect regulatory cascades mediated by NF-кB and Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling. NRF1 and GABPA seem to be the main regulators of the transcriptional profile observed after RESV treatment.pt_BR
dc.identifier.citationPINHEIRO, D. M. L. et al. Resveratrol decreases the expression of genes involved in inflammation through transcriptional regulation. Free Radic Biol Med., v. 130, p. 8-22, out. 2018. doi: 10.1016/j.freeradbiomed.2018.10.432pt_BR
dc.identifier.doi10.1016/j.freeradbiomed.2018.10.432
dc.identifier.urihttps://repositorio.ufrn.br/jspui/handle/123456789/26434
dc.languageengpt_BR
dc.rightsAcesso Abertopt_BR
dc.subjectChromatinpt_BR
dc.subjectinflammationpt_BR
dc.subjectRNAseqpt_BR
dc.subjectresveratrolpt_BR
dc.subjecttranscriptionpt_BR
dc.titleResveratrol decreases the expression of genes involved in inflammation through transcriptional regulationpt_BR
dc.typearticlept_BR

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