Modulation of Cytokine Production and Transcription Factors Activities in Human Jurkat T Cells by Thymol and Carvacrol

Abstract

Purpose: Thymol and carvacrol, two main components of thyme, have shown anti-inflammatory effects. The aim of this study was to assess the effects of these components on Jurkat leukemia cells as an in vitro T cell model and their molecular mechanisms of activity. Methods: Cells were cultured in the presence of components and subsequently stimulated with phorbol-12-myristate-13-acetate (PMA)/calcium ionophore for evaluating interleukin (IL)-2 and interferon (IFN)-gamma production. The activation of T cell transcription factors that included nuclear factors of activated T cells (NFATs), activator protein-1 (AP-1; c-Jun/cFos), and nuclear factor (NF)-kappa B were examined by Western blot analysis. Results: Thymol and carvacrol at 25 mu g/ml significantly reduced IL-2 levels from 119.4 +/- 8pg/ml in control cells treated only with PMA/Calcium ionophore and the solvent to 66.9 +/- 6.4pg/ml (thymol) and 32.3 +/- 3.6pg/ml (carvacrol) and IFN-gamma from 423.7 +/- 19.7pg/ml in control cells to 311.9 +/- 11.6pg/ml (thymol) and 293.5 +/- 16.7pg/ml (carvacrol). Western blot analyses of nuclear extracts showed that the same concentrations of components significantly reduced NFAT-2 to 44.2 +/- 2.7 (thymol) and 91.4 +/- 2.3 (carvacrol) of the control (p<0.05), and c-Fos to 31.2 +/- 6.2 (thymol) and 27.6 +/- 3.1 (carvacrol) of the control (p<0.01). No effects on NFAT-1, c-Jun and phospho-NF-kappa Bp65 levels were observed. Conclusion: Thymol and carvacrol could contribute to modulation of T cell activity by reducing IL-2 and IFN-gamma production possibly through down regulation of AP-1 and NFAT-2 transcription factors suggesting their potential usefulness for reduction of T cell overactivity in immune-mediated diseases.