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06.10 Effects of resveratrol and a resveratrol-salicylate hybrid molecule on activation of human cd4+ t- cells
  1. Katrin Goldhahn1,
  2. Burkhard Kloesch1,
  3. Farid Aldawsari2,
  4. Carlos Velazques-Martinez2,
  5. Klaus Schmetterer3,
  6. Guenter Steiner1,4
  1. 1Ludwig Boltzmann Cluster for Arthritis and Rehabilitation, Department for Degenerative Joint Diseases 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, Austria
  4. 4Medical University Vienna, Department of Internal Medicine III, Division of Rheumatology, Austria

Abstract

Background 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. Consequently, substances modulating T-cell activation may have therapeutic benefit in RA and related rheumatic diseases. 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 compare the effects of resveratrol and a novel resveratrol-salicylate hybrid molecule (C10) on human CD4+ T-cells.

Methods CD4+ T-cells were isolated from healthy donors and pre-incubated with different concentrations of resveratrol or C-10 before being stimulated with anti-CD3/anti-CD28 antibodies. After 24 hour and 72 hour, 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 western blot 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 as compared to resveratrol. Thus, a decrease of cytokine expression was observed already at 6.25 µM C-10 whereas resveratrol inhibited cytokine production only at 25 µM or 50 µM significantly. Moreover, the proliferation rate was significantly more decreased in the presence of C-10. The expression of CD25, CD69, CD71 and CD98hc was reduced to a similar degree by both compounds. Furthermore, phosphorylation of ERK, Akt and S6RP was attenuated when the cells were incubated with resveratrol or C-10.

Conclusion Our data demonstrate that C-10 suppressed cytokine secretion and proliferation more effectively than resveratrol. Both compounds influence the phosphorylation of important signalling molecules. Thus, the resveratrol-salicylate hybrid molecule C-10 significantly amplified the effects of resveratrol in CD4+ T- cells and might be used in the future for treatment of RA and other T-cell driven autoimmune diseases.

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