Resveratrol as a natural anti-tumor necrosis factor-α molecule: implications to dendritic cells and their crosstalk with mesenchymal stromal cells

PLoS One. 2014 Mar 10;9(3):e91406. doi: 10.1371/journal.pone.0091406. eCollection 2014.

Abstract

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 µM) reduce cell activation in response to tumor necrosis factor (TNF)-α, significantly decreasing surface expression of CD83 and CD86. Functionally, IL-12/IL-23 secretion induced by TNF-α was significantly reduced by resveratrol, while IL-10 levels increased. Resveratrol also inhibited T cell proliferation, in response to TNF-α-stimulated DC. The underlying mechanism was investigated by Western blot and imaging flow cytometry (ImageStreamX), and likely involves impairment of nuclear translocation of the p65 NF-κB subunit. Importantly, results obtained demonstrate that DC are able to recruit MSC through extracellular matrix components, and that TNF-α 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-α further decreased MSC motility, while resveratrol recovered it. Thus, the current study points out the potential of resveratrol as a natural anti-TNF-α drug, capable of modulating DC phenotype and function, as well as DC-mediated MSC recruitment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Death / drug effects
  • Cell Differentiation / drug effects
  • Cell Movement / drug effects
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Cell Proliferation / drug effects
  • Coculture Techniques
  • Cytokines / metabolism
  • Dendritic Cells / cytology
  • Dendritic Cells / drug effects
  • Dendritic Cells / metabolism*
  • Humans
  • Inflammation / pathology
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism*
  • NF-kappa B / metabolism
  • Phenotype
  • Protein Transport / drug effects
  • Resveratrol
  • Signal Transduction / drug effects
  • Stilbenes / pharmacology*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Cytokines
  • NF-kappa B
  • Stilbenes
  • Tumor Necrosis Factor-alpha
  • Resveratrol