Lima, Lucymara Fassarella AgnezPinheiro, Daniele Maria Lopes2019-03-132019-03-132018-11-09PINHEIRO, Daniele Maria Lopes. Efeito do Resveratrol frente à resposta inflamatória no modelo celular U937. 2018. 200f. Tese (Doutorado em Ciências da Saúde) - Centro de Ciências da Saúde, Universidade Federal do Rio Grande do Norte, Natal, 2018.https://repositorio.ufrn.br/jspui/handle/123456789/26765The so-called oxidative stress seems to be a trigger for the development of numerous pathologies. In this scenario, the inflammatory response may become a villain for homeostasis, putting cell and nuclear signaling pathways at risk. Faced with this, the effort to reduce the sequelae of dysfunctional metabolic pathways has gained strength. Currently, many studies have proposed the use of polyphenols to reduce an exacerbated inflammatory response. Resveratrol is a potent target because of its antioxidant activity and important biological functions. It is known to exert cardioprotective, anti-cancer, anti-inflammatory, neuroprotective activities. In this context, in order to better elucidate how this antioxidant regulates inflammation, and to reveal the gene transcription profile during the inflammatory response in cells exposed to Resveratrol, U937 monocytic cells were used. Cells were stimulated with LPS for 24 h e co-incubated with Resveratrol (15 μM) for 4 h. Our results showed that the polyphenol studied was not able to alter cell viability as well as to induce programmed cell death by cell viability and apoptosis assays. Through Genome-wide RNA sequencing by 454 platform was revealed 8.671 differentially expressed genes, with fold change ≥2.0 and ≤-2.0 being analyzed. The upregulated genes were mostly associated to transcription, metabolic processes, immune system and cell cycle, while the downregulated genes were associated to processes as inflammatory response, transcription and chromatin remodeling. Comparing the transcriptome data with an in vitro analysis by immunoprecipitation and protein expression, we observed that Resveratrol is able to modulate epigenetic features as of histones and nonhistones acetylation and methylation. For the first time a decrease in APE1/Ref-1 acetylation pattern was observed without affecting your repair activity. In summary, this study elucidated important biological processes related to the anti-inflammatory effect of Resveratrol, showing that it acts on the transcriptional regulation of genes related to inflammation.Acesso AbertoResveratrolInflamaçãoRNAseqCromatinaTranscriçãodoctoralThesisCNPQ::CIENCIAS DA SAUDE