Pioglitazone, a PPAR- Agonist, Downregulates Cytokine Production and AP-1 DNA-Binding Protein in Human Peripheral Blood T Cells – Potential Implication in the Treatment of Atherosclerotic Disease

Background: Atherosclerotic cardiovascular diseases are known to be inflammatory ones. In atherosclerotic lesions, T lymphocytes resulted in the vascular inflammatory reactions by producing many proinflammatory cytokines. Peroxisome proliferator-activated receptor-gamma (PPAR) agonists, insulin sensitizers, exhibit antiinflammatory effects in various types of cells and may have anti-atherosclerotic actions. Aim: To determine whether pioglitazone exhibits anti-inflammatory actions in vitro, we examined the effects of pioglitazone in human peripheral T cells. Methods: The purified drug “pioglitazone” was prepared in solution with different concentrations. Human peripheral blood T cells were purified from the buffy coat of whole blood. For cell activation, PMA and ionomycin were used. Cytokines were measured by ELISA, and activator protein-1 (AP-1) DNA binding activity was detected by electrophoretic mobility shift assays in activated T cells which were either pretreated with pioglitazone or not. Results: We demonstrated that pioglitazone inhibited the production of IL-2, IL4, IFN, and TNFfrom activated T cells. Molecular investigation indicated that pioglitazone downregulated the activity of AP-1 DNA binding protein in stimulated T lymphocytes. Conclusion: In this in-vitro study, pioglitazone might have had some anti-inflammatory effects on human peripheral T lymphocytes via regulation of both cytokine production and AP-1 DNA binding activity.