Resveratrol decreases the expression of genes involved in inflammation through transcriptional regulation
| Autor: | Andre Luis Fonseca Faustino, Thais Teixeira Oliveira, Fabrícia Lima Fontes, Vandeclecio Lira da Silva, Daniele Maria Lopes Pinheiro, Sandro J. de Souza, Lucymara Fassarella Agnez-Lima, Leonam Gomes Coutinho, Julliane Tamara Araújo de Melo Campos, Ana Helena Sales de Oliveira, Tirzah Braz Petta Lajus, Rayssa Karla de Medeiros Oliveira |
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| Rok vydání: | 2019 |
| Předmět: |
Lipopolysaccharides
0301 basic medicine Anti-Inflammatory Agents resveratrol Biochemistry Antioxidants Monocytes 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Physiology (medical) Histone methylation Gene expression Transcriptional regulation Humans NRF1 Inflammation biology Nuclear Respiratory Factor 1 Sequence Analysis RNA Chemistry Gene Expression Profiling NF-kappa B Acetylation U937 Cells RNAseq GA-Binding Protein Transcription Factor Chromatin Cell biology Oxidative Stress Gene Ontology 030104 developmental biology Gene Expression Regulation Resveratrol inflammation biology.protein Cytokines Demethylase Tumor necrosis factor alpha Inflammation Mediators transcription Janus kinase 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Repositório Institucional da UFRN Universidade Federal do Rio Grande do Norte (UFRN) instacron:UFRN |
| ISSN: | 0891-5849 |
| DOI: | 10.1016/j.freeradbiomed.2018.10.432 |
| Popis: | 2020-01-01 Oxidative 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. |
| Databáze: | OpenAIRE |
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