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 language | English |
|---|---|
| Pages (from-to) | 32-36 |
| Number of pages | 5 |
| Journal | Transplant Immunology |
| Volume | 18 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jul 2007 |
Fingerprint
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 journal › Article
}
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 -