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

7 Citations (Scopus)

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

Fingerprint

Peroxisome Proliferator-Activated Receptors
Immunosuppressive Agents
Cyclosporine
T-Lymphocytes
Interleukin-2
rosiglitazone
Cell Proliferation
Ligands
Cell Cycle
Mixed Lymphocyte Culture Test
In Vitro Techniques
Interleukin-2 Receptors
Cytoplasmic and Nuclear Receptors
Helper-Inducer T-Lymphocytes
Mitogens
Lipid Metabolism
Immunosuppression
Thymidine
Blood Cells
Enzyme-Linked Immunosorbent Assay

Keywords

  • Cyclosporine
  • PPARgamma
  • Transplantation

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Transplantation

Cite this

Activation of PPARγ enhances in vitro the immunosuppressive effect of cyclosporine on T lymphocytes. / Rampino, Teresa; Ranghino, Andrea; Guidetti, Cristina; Gregorini, Marilena; Soccio, Grazia; Marasà, Maddalena; Libetta, Carmelo; Guida, Gianenrico; De Amici, Mara; Dal Canton, Antonio.

In: Transplant Immunology, Vol. 18, No. 1, 07.2007, p. 32-36.

Research output: Contribution to journalArticle

Rampino, Teresa ; Ranghino, Andrea ; Guidetti, Cristina ; Gregorini, Marilena ; Soccio, Grazia ; Marasà, Maddalena ; Libetta, Carmelo ; Guida, Gianenrico ; De Amici, Mara ; Dal Canton, Antonio. / Activation of PPARγ enhances in vitro the immunosuppressive effect of cyclosporine on T lymphocytes. In: Transplant Immunology. 2007 ; Vol. 18, No. 1. pp. 32-36.
@article{411667f41c044190b93c036b566b0724,
title = "Activation of PPARγ enhances in vitro the immunosuppressive effect of cyclosporine on T lymphocytes",
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.",
keywords = "Cyclosporine, PPARgamma, Transplantation",
author = "Teresa Rampino and Andrea Ranghino and Cristina Guidetti and Marilena Gregorini and Grazia Soccio and Maddalena Maras{\`a} and Carmelo Libetta and Gianenrico Guida and {De Amici}, Mara and {Dal Canton}, Antonio",
year = "2007",
month = "7",
doi = "10.1016/j.trim.2007.03.003",
language = "English",
volume = "18",
pages = "32--36",
journal = "Transplant Immunology",
issn = "0966-3274",
publisher = "Elsevier",
number = "1",

}

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

UR - http://www.scopus.com/inward/record.url?scp=34250613532&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34250613532&partnerID=8YFLogxK

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 -