Peroxisome Proliferator-Activated Receptor gamma (PPARgamma) is a nuclear receptor that regulates the transcription of genes associated with lipid and glucose metabolism. Recently, it has been shown that PPARgamma modulates the activity of T cells, resulting in inhibition of T cell proliferation and IL-2 release. In this study we investigated whether the PPARgamma ligand rosiglitazone (R) enhances in vitro the immunosuppressive effects of cyclosporine A (CsA).CD4(+) T cells isolated from peripheral blood mononuclear cells of healthy donors were activated either with mitogens or by one-way mixed lymphocyte reaction. The activated T cells were treated with (1) CsA at low and high concentration (50, 150 ng/ml); (2) R (20 muM); (3) R (20 muM) in combination with CsA at low concentration (50 ng/ml). We studied the effects of the various treatments on cell proliferation (incorporation of [(3)H] thymidine), the cell-cycle phases (FACS analysis), IL-2 release (ELISA), and IL-2 receptor (CD25) expression (FACS analysis).R used alone reduced T cell proliferation and CD25 expression. Low-dose CsA combined with R was significantly more powerful than either high-dose CsA alone or R alone in suppressing IL-2 release, arresting the T cell cycle, and blocking the growth of activated T cells.PPARgamma ligand R potentiates in vitro the inhibitory action of CsA on activated T helper cells. The combined use of PPARgamma ligands and low-dose CsA represents a rationale therapeutic approach aimed to prevent CsA nephrotoxicity while maintaining adequate immunosuppression.

Activation of PPARgamma enhances in vitro the immunosuppressive effect of cyclosporine on T lymphocytes.

RAMPINO, TERESA;GREGORINI, MARILENA;LIBETTA, CARMELO;DAL CANTON, ANTONIO;DE AMICI, MARA
2007

Abstract

Peroxisome Proliferator-Activated Receptor gamma (PPARgamma) is a nuclear receptor that regulates the transcription of genes associated with lipid and glucose metabolism. Recently, it has been shown that PPARgamma modulates the activity of T cells, resulting in inhibition of T cell proliferation and IL-2 release. In this study we investigated whether the PPARgamma ligand rosiglitazone (R) enhances in vitro the immunosuppressive effects of cyclosporine A (CsA).CD4(+) T cells isolated from peripheral blood mononuclear cells of healthy donors were activated either with mitogens or by one-way mixed lymphocyte reaction. The activated T cells were treated with (1) CsA at low and high concentration (50, 150 ng/ml); (2) R (20 muM); (3) R (20 muM) in combination with CsA at low concentration (50 ng/ml). We studied the effects of the various treatments on cell proliferation (incorporation of [(3)H] thymidine), the cell-cycle phases (FACS analysis), IL-2 release (ELISA), and IL-2 receptor (CD25) expression (FACS analysis).R used alone reduced T cell proliferation and CD25 expression. Low-dose CsA combined with R was significantly more powerful than either high-dose CsA alone or R alone in suppressing IL-2 release, arresting the T cell cycle, and blocking the growth of activated T cells.PPARgamma ligand R potentiates in vitro the inhibitory action of CsA on activated T helper cells. The combined use of PPARgamma ligands and low-dose CsA represents a rationale therapeutic approach aimed to prevent CsA nephrotoxicity while maintaining adequate immunosuppression.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11571/220981
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