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  • Title: Transforming growth factor-beta1 inhibits vascular permeability factor release by T cells in normal subjects and in patients with minimal-change nephrotic syndrome.
    Author: Matsumoto K, Kanmatsuse K.
    Journal: Nephron; 2001 Feb; 87(2):111-7. PubMed ID: 11244304.
    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.
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