Resveratrol as a Natural Anti-Tumor Necrosis Factor-[alpha] Molecule: Implications to Dendritic Cells and Their Crosstalk with Mesenchymal Stromal Cells

• Published in: PloS one Vol. 9; no. 3; p. e91406
• Main Authors: Silva, Andreia M, Oliveira, Marta I, Sette, Laura, Almeida, Catarina R, Oliveira, Maria J, Barbosa, Mário A, Santos, Susana G
• Format: Journal Article
• Language: English
• Published: Public Library of Science 10.03.2014
• Subjects: Anti-inflammatory agents; Dendritic cells; Necrosis; Resveratrol; Stem cells; T cells; Tumor necrosis factor; Tumors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0091406

Dendritic cells (DC) are promising targets for inducing tolerance in inflammatory conditions. Thus, this study aims to investigate the effects of the natural anti-inflammatory molecule resveratrol on human DC at phenotypic and functional levels, including their capacity to recruit mesenchymal stem/stromal cells (MSC). Primary human monocyte-derived DC and bone marrow MSC were used. DC immunophenotyping revealed that small doses of resveratrol (10 [micro]M) reduce cell activation in response to tumor necrosis factor (TNF)-[alpha], significantly decreasing surface expression of CD83 and CD86. Functionally, IL-12/IL-23 secretion induced by TNF-[alpha] was significantly reduced by resveratrol, while IL-10 levels increased. Resveratrol also inhibited T cell proliferation, in response to TNF-[alpha]-stimulated DC. The underlying mechanism was investigated by Western blot and imaging flow cytometry (ImageStream.sup.X ), and likely involves impairment of nuclear translocation of the p65 NF-[kappa]B subunit. Importantly, results obtained demonstrate that DC are able to recruit MSC through extracellular matrix components, and that TNF-[alpha] impairs DC-mediated recruitment. Matrix metalloproteinases (MMP) produced by both cell populations were visualized by gelatin zymography. Finally, time-lapse microscopy analysis revealed a significant decrease on DC and MSC motility in co-cultures, indicating cell interaction, and TNF-[alpha] further decreased MSC motility, while resveratrol recovered it. Thus, the current study points out the potential of resveratrol as a natural anti-TNF-[alpha] drug, capable of modulating DC phenotype and function, as well as DC-mediated MSC recruitment.