title: The anti-inflammatory effects of resveratrol on human peripheral blood mononuclear cells are influenced by a superoxide dismutase 2 gene polymorphism.
abstract: Resveratrol is an molecule that provides both anti-inflammatory and antioxidant properties. However, it is unclear whether the basal oxidative state of the cell has any influence on the effects of this compound. In humans, a single nucleotide polymorphism (SNP) is present in the enzyme manganese superoxide dismutase (SOD2), localized in codon 16 (rs4880), which can either be an alanine (A) or valine (V). This SNP causes an imbalance in the cellular levels of SOD2, where AA- and VV-genotypes result in higher or lower enzymatic activity, respectively. Furthermore, the VV-genotype has been associated with high levels of inflammatory cytokines. Here, we examined the effects of a range of resveratrol concentrations on the in vitro activation of human peripheral blood mononuclear cells (PBMCs) carrying different Ala16Val-SOD2 genotypes. Cell proliferation, several oxidative biomarkers and cytokines (IL-1β, IL-6, TNFα, Igγ and IL-10) were analyzed. In addition, the effects of resveratrol on the expression of the sirt1 gene were evaluated by qRT-PCR. After 24 h exposure to resveratrol, A-genotype PBMCs displayed a decrease in cell proliferation, whilst VV-cells contrasted; At 10 µM resveratrol, there was a significant decrease in the production of inflammatory cytokines in A-allele cells; however, VV-cells generally displayed a subtle decrease in these, except for TNFα, which was not affected. In all SOD2 genotypes cells exposed to resveratrol resulted in an upregulation of Sirt1 levels. Together, these results suggest that the effect of resveratrol on human PBMC activation is not universal and is dependent on the Ala16Val-SOD2 SNP.
authors.affiliation: Pharmacology Graduate Program, Federal University of Santa Maria (UFSM), Av. Roraima 1000, Prédio 19, Santa Maria, RS, 90105900, Brazil.
authors.forename: Dianni
authors.initials: D
authors.lastname: Capeleto
authors.forename: Fernanda
authors.initials: F
authors.lastname: Barbisan
authors.forename: Verônica
authors.initials: V
authors.lastname: Azzolin
authors.forename: Eduardo Bortoluzzi
authors.initials: EB
authors.lastname: Dornelles
authors.forename: Felipe
authors.initials: F
authors.lastname: Rogalski
authors.forename: Cibele Ferreira
authors.initials: CF
authors.lastname: Teixeira
authors.forename: Alencar Kolinski
authors.initials: AK
authors.lastname: Machado
authors.forename: Francine Carla
authors.initials: FC
authors.lastname: Cadoná
authors.forename: Tális
authors.initials: T
authors.lastname: da Silva
authors.forename: Thiago
authors.initials: T
authors.lastname: Duarte
authors.forename: Marta Maria Medeiros Frescura
authors.initials: MM
authors.lastname: Duarte
authors.forename: Ivana Beatrice Mânica
authors.initials: IB
authors.lastname: da Cruz
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005838:Genotype; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D018384:Oxidative Stress / Q000187:drug effects; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism; D000099156:Superoxide Dismutase 2
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D016207:Cytokines; D018836:Inflammation Mediators; D000077185:Resveratrol; D056564:Sirtuin 1; D013267:Stilbenes; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C447939:SIRT1 protein, human