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

Teresa Rampino, Andrea Ranghino, Cristina Guidetti, Marilena Gregorini, Grazia Soccio, Maddalena Marasà, Carmelo Libetta, Gianenrico Guida, Mara De Amici, Antonio Dal Canton

Research output: Contribution to journalArticle

Abstract

Background: Peroxisome Proliferator-Activated Receptor γ (PPARγ) is a nuclear receptor that regulates the transcription of genes associated with lipid and glucose metabolism. Recently, it has been shown that PPARγ modulates the activity of T cells, resulting in inhibition of T cell proliferation and IL-2 release. In this study we investigated whether the PPARγ ligand rosiglitazone (R) enhances in vitro the immunosuppressive effects of cyclosporine A (CsA). Methods: 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 μM); (3) R (20 μM) in combination with CsA at low concentration (50 ng/ml). We studied the effects of the various treatments on cell proliferation (incorporation of [3H] thymidine), the cell-cycle phases (FACS analysis), IL-2 release (ELISA), and IL-2 receptor (CD25) expression (FACS analysis). Results: 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. Conclusion: PPARγ ligand R potentiates in vitro the inhibitory action of CsA on activated T helper cells. The combined use of PPARγ ligands and low-dose CsA represents a rationale therapeutic approach aimed to prevent CsA nephrotoxicity while maintaining adequate immunosuppression.

Original languageEnglish
Pages (from-to)32-36
Number of pages5
JournalTransplant Immunology
Volume18
Issue number1
DOIs
Publication statusPublished - Jul 2007

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Keywords

  • Cyclosporine
  • PPARgamma
  • Transplantation

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Transplantation

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