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In vivo expression of transforming growth factor-beta1 in humans: stimulation by cyclosporine.

Authors
Shin, GT; Khanna, A; Ding, R; Sharma, VK; Lagman, M; Li, B; Suthanthiran, M
Citation
Transplantation, 65(3):313-318, 1998
Journal Title
Transplantation
ISSN
0041-13371534-6080
Abstract
BACKGROUND: Transforming growth factor-beta1 (TGF-beta1) is an immunoregulatory and fibrogenic cytokine. In an earlier in vitro study, we demonstrated that cyclosporine (CsA) increases TGF-beta1 transcription rate in human T lymphocytes. Herein, we explored whether CsA augments the in vivo expression of TGF-beta1 in humans.



METHODS: The inherent difficulty in studying the in vivo effect of CsA in humans was circumvented by investigating stable end-stage renal disease patients who were preconditioned with CsA before their living donor renal transplantation. Sera and peripheral blood mononuclear cells were obtained from CsA-preconditioned patients and quantified for TGF-beta1 expression at the mRNA (by competitive polymerase chain reaction) and protein (sandwich enzyme-linked immunosorbent assay) levels.



RESULTS: Our studies demonstrated a significant increase in TGF-beta1 expression after CsA therapy. The stimulatory effect was unique to TGF-beta1, and CsA did not increase interleukin (IL)-10, IL-6, IL-2, or tumor necrosis factor-alpha expression.



CONCLUSIONS: Our first-time demonstration of a TGF-beta1-selective in vivo stimulatory effect of CsA in humans: (1) advances a TGF-beta1-centered hypothesis for the beneficial (immunosuppression) and detrimental (fibrosis, hypertension) effects of CsA use, and (2) broadens the mechanism of immunosuppressive action of CsA to include heightened expression of an endogenous immunosuppressive cytokine.
MeSH terms
Cyclosporine/*therapeutic useHumansImmunosuppressive Agents/*therapeutic useInterleukin-10/biosynthesis/bloodInterleukin-2/biosynthesis/bloodInterleukin-6/biosynthesis/bloodKidney Failure, Chronic/blood/*immunology/surgeryKidney Transplantation/immunologyLiving DonorsPolymerase Chain ReactionT-Lymphocytes/drug effects/*immunologyTranscription, Genetic/drug effectsTransforming Growth Factor beta/*biosynthesis/bloodTumor Necrosis Factor-alpha/biosynthesis
PMID
9484745
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Nephrology
AJOU Authors
신, 규태
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