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A7.11 Resveratrol and a resveratrol-salicylate hybrid molecule suppress cytokine production and proliferation of human CD4+ T-cells
  1. K Goldhahn1,
  2. B Kloesch1,
  3. F Aldawsari2,
  4. C Velazquez-Martinez2,
  5. K Schmetterer3,
  6. G Steiner1,4
  1. 1Ludwig Boltzmann Cluster for Rheumatology and Rehabilitation, Department for Degenerative Joint Disease, Vienna, Austria
  2. 2University of Alberta, Katz Group Centre for Pharmacy and Health Research, Edmonton Alberta, Canada
  3. 3Medical University of Vienna, Department of Laboratory Medicine, Vienna, Austria
  4. 4Medical University of Vienna, Department of Internal Medicine III, Division of Rheumatology, Vienna, Austria

Abstract

Introduction Aberrant T-cell responses are crucially involved in the pathogenesis of systemic autoimmune diseases such as rheumatoid arthritis (RA) leading to chronic inflammation and organ damage. Resveratrol is a natural occuring polyphenol mainly produced in plants. The beneficial effects of resveratrol are due to its anti-inflammatory, anti-carcinogenic and anti-oxidant activities. The aim of this study was to investigate the effects of resveratrol and a novel resveratrol-salicylate hybrid molecule (C10) on human CD4+ T-cells.

Methods CD4+ T-cells from healthy donors were pre-incubated with different concentrations of resveratrol or C-10 before being stimulated with anti-CD3/anti-CD28 antibodies. After 24 h and 72 h, respectively, cell culture supernatants were harvested and IL-2, IFN-γ and TNF-α release were quantified by ELISA. Proliferation rate was measured by thymidine incorporation. In addition, the up-regulation of the early activation markers CD25, CD69, CD71 and CD98 was analysed and phosphorylation of the MAP-kinase ERK as well as AKT and SRP6 was determined by westernblot or flow cytometry.

Results Inhibition of IL-2, IFN-γ and TNF-α release was significantly more effective when the cells were treated with C-10 (p < 0.05). In comparison to the untreated control, C-10 inhibited cytokine production by 35% (6.25 µM), by 55% (12.5 µM) or by 80% (25 µM) whereas resveratrol inhibited cytokine production only at 25 µM or 50 µM significantly. Moreover, proliferation rate in CD4+ T-cells was significantly more decreased in the presence of C-10 at concentrations of 25 µM or 50 µM (p < 0.0001). The expression of the early activation markers CD25, CD69, CD71 and CD98 was reduced in a dose dependent manner when the cells were exposed to resveratrol or C-10. Furthermore, the phosphorylation of ERK, Akt and S6RP was attenuated by resveratrol or C-10 to a similar degree.

Conclusion Resveratrol and C-10 both suppressed cytokine secretion and proliferation of CD4+ T-cells. The suppressive effects appear to be based on partial suppression of phosphorylation of several important signalling molecules involved in cytokine expression and cell growth. Since C-10 significantly amplified the effects of resveratrol these data suggest C-10 as an interesting candidate drug for treatment of RA and other T cell driven autoimmune diseases.

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