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Cyclosporine induces the expression of the cyclin inhibitor p21

A K Khanna1, J D Hosenpud

  • 1Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee 53226, USA. akkhanna@mcw.edu

Transplantation
|May 26, 1999
PubMed
Abstract

Insights

Cyclosporine A (CsA) suppresses T cell proliferation by increasing the cell cycle inhibitor p21, a process dependent on transforming growth factor-beta (TGF-beta). Inducing p21 independently of TGF-beta may reduce immunosuppression toxicity.

Area of Science:

  • Immunology
  • Cell Biology
  • Pharmacology

Background:

  • Current immunosuppression targets T cell activation and proliferation.
  • Cyclosporine A (CsA) is an immunosuppressant.
  • Cell cycle progression involves cyclins and cyclin-dependent kinases.

Purpose of the Study:

  • To investigate if CsA suppresses cell cycle progression via p21 induction.
  • To determine if CsA's p21 induction is dependent on transforming growth factor-beta (TGF-beta).

Main Methods:

  • Reverse transcription PCR and Western blot to assess p21 mRNA and protein.
  • Luciferase assay to study p21 promoter activity.
  • Use of anti-TGF-beta antibody and TGF-beta altered cells to assess dependence.

Main Results:

  • CsA induced p21 mRNA, protein expression, and promoter activity in T cells and A-549 cells.
  • CsA's induction of p21 was inhibited by anti-TGF-beta antibody.
  • Effects on p21 required TGF-beta, as shown in TGF-beta altered cells.

Conclusions:

  • CsA's antiproliferative effects involve p21 induction, which is dependent on TGF-beta.
  • Inducing p21 independently of TGF-beta could mitigate immunosuppression toxicity.

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