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Article History
Submitted: 17 May 2015
Revised: 20 Sep 2015
Accepted: 29 Oct 2015
First published online: 31 Dec 2015

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Adv Pharm Bull. 2015;5(5):653-660 doi: 10.15171/apb.2015.089
PMID:26793612        PMCID:PMC4708037

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

Original Research

Nasser Gholijani 1, Marjan Gharagozloo 2,3, Fathollah Kalantar 4, Amin Ramezani 5,6, Zahra Amirghofran 4,7 *

1 Autoimmune Diseases Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
2 Department of Immunology, Isfahan University of Medical Sciences, Isfahan, Iran.
3 Department of Pediatrics, CR-CHUS, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke,Quebec,Canada.
4 Department of Immunology, Shiraz University of Medical Sciences, Shiraz, Iran.
5 Department of Medical Biotechnology, School of Advanced Medical Sciences and Technology, Shiraz University of Medical Sciences, Shiraz, Iran.
6 Institute for Cancer Research, Shiraz University of Medical sciences, Shiraz, Iran.
7 Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.



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)-γ production. The activation of T cell transcription factors that included nuclear factors of activated T cells (NFATs), activator protein-1 (AP-1; c-Jun/c-Fos), and nuclear factor (NF)-KB were examined by Western blot analysis. Results: Thymol and carvacrol at 25 µg/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-γ 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-KBp65 levels were observed. Conclusion: Thymol and carvacrol could contribute to modulation of T cell activity by reducing IL-2 and IFN-γ 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.





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