Transforming growth factor-beta1 inhibits vascular permeability factor release by T cells in normal subjects and in patients with minimal-change nephrotic syndrome

Nephron. 2001 Feb;87(2):111-7. doi: 10.1159/000045898.

Abstract

Background/aim: A lymphokine, the vascular permeability factor (VPF), which increases vascular permeability, has been characterized in minimal-change nephrotic syndrome (MCNS). Transforming growth factor-beta (TGF-beta) is an immunosuppressive cytokine that inhibits proliferation, cytokine production, and cytotoxic activity of T cells and natural killer cells. We, therefore, investigated the effects of TGF-beta1 on the release of VPF by peripheral blood T cells from MCNS patients. The aim of our study was to determine the in vitro immunosuppressive capacity of TGF-beta1 in patients with MCNS.

Methods: To further test the effect of TGF-beta1 on concanavalin A (Con A)-induced VPF release, normal and MCNS T cells were stimulated with 5 microg/ml of Con A in the presence or absence of TGF-beta1, and the culture supernatants were tested for the presence of VPF by the method of Lagrue et al. The disease controls included 16 patients with IgA nephropathy.

Results: Significantly increased spontaneous and Con A-stimulated secretion of VPF was detected in T-cell cultures of MCNS patients with the nephrotic syndrome as compared with those of normal controls. Addition of TGF-beta1 to these cultures inhibited the release of VPF in a dose-dependent manner. The effect of TGF-beta1 on the release of VPF was specific, since a reversion was obtained with a neutralizing monoclonal antibody to human TGF-beta1.

Conclusion: Together, our data demonstrate that TGF-beta1 antagonizes the ability of T cells to release VPF, and suggest a role of TGF-beta1 in the pathophysiology of VPF in vitro.

MeSH terms

  • Adult
  • Capillary Permeability
  • Case-Control Studies
  • Concanavalin A / pharmacology
  • Dose-Response Relationship, Drug
  • Endothelial Growth Factors / metabolism*
  • Female
  • Glomerulonephritis, IGA / physiopathology
  • Glucocorticoids / pharmacology
  • Humans
  • In Vitro Techniques
  • Lymphokines / metabolism*
  • Male
  • Nephrosis, Lipoid / drug therapy
  • Nephrosis, Lipoid / physiopathology*
  • Prednisone / pharmacology
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / metabolism*
  • Transforming Growth Factor beta / administration & dosage
  • Transforming Growth Factor beta / antagonists & inhibitors
  • Transforming Growth Factor beta / pharmacology*
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • Endothelial Growth Factors
  • Glucocorticoids
  • Lymphokines
  • Transforming Growth Factor beta
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Concanavalin A
  • Prednisone