TY - JOUR
T1 - Activation of PPARγ enhances in vitro the immunosuppressive effect of cyclosporine on T lymphocytes
AU - Rampino, Teresa
AU - Ranghino, Andrea
AU - Guidetti, Cristina
AU - Gregorini, Marilena
AU - Soccio, Grazia
AU - Marasà, Maddalena
AU - Libetta, Carmelo
AU - Guida, Gianenrico
AU - De Amici, Mara
AU - Dal Canton, Antonio
PY - 2007/7
Y1 - 2007/7
N2 - 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.
AB - 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.
KW - Cyclosporine
KW - PPARgamma
KW - Transplantation
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U2 - 10.1016/j.trim.2007.03.003
DO - 10.1016/j.trim.2007.03.003
M3 - Article
C2 - 17584600
AN - SCOPUS:34250613532
VL - 18
SP - 32
EP - 36
JO - Transplant Immunology
JF - Transplant Immunology
SN - 0966-3274
IS - 1
ER -