In vivo hyperexpression of transforming growth factor-β1 in mice

Stimulation by cyclosporine

Ashwani Khanna, Sandip Kapur, Vijay Sharma, Baogui Li, Manikkam Suthanthiran

Research output: Contribution to journalArticle

95 Citations (Scopus)

Abstract

Background. We have demonstrated that cyclosporine (CsA) stimulates transforming growth factor (TGF) β1 expression in vitro and that growth of mammalian cells can be arrested by CsA via a TGF-β1-dependent mechanism. Herein, we have explored whether CsA stimulates TGF-β1 hyperexpression in vivo. Methods. Four groups of B6AF1 mice were studied: group 1, control; group 2, CsA pretreatment; group 3, anti-CD3 monoclonal antibody pretreatment; and group 4, CsA plus anti-CD3 pretreatment. Results. CsA pretreatment augmented TGF-β1 protein expression and increased intrarenal display of TGF-β1 mRNA. This heightened TGF-β1 expression was associated with an impaired T cell proliferative response. Conclusions. Our observations, together, advance the hypothesis that CsA might function in viva as an immunosuppressant not only by inhibiting the expression of proinflammatory cytokines (e.g., interleukin 2), but also by stimulating the expression of TGF-β1, a potent immunosuppressive cytokine. Moreover, prevention of TGF-β1 hyperexpression might prevent CsA-associated renal fibrosis, as TGF-β1 is a fibrogenic cytokine.

Original languageEnglish
Pages (from-to)1037-1039
Number of pages3
JournalTransplantation
Volume63
Issue number7
DOIs
Publication statusPublished - 15 Apr 1997
Externally publishedYes

Fingerprint

Transforming Growth Factors
Cyclosporine
Immunosuppressive Agents
Cytokines
Interleukin-2
Fibrosis
Monoclonal Antibodies
T-Lymphocytes
Kidney
Control Groups
Messenger RNA
Growth

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

In vivo hyperexpression of transforming growth factor-β1 in mice : Stimulation by cyclosporine. / Khanna, Ashwani; Kapur, Sandip; Sharma, Vijay; Li, Baogui; Suthanthiran, Manikkam.

In: Transplantation, Vol. 63, No. 7, 15.04.1997, p. 1037-1039.

Research output: Contribution to journalArticle

Khanna, Ashwani ; Kapur, Sandip ; Sharma, Vijay ; Li, Baogui ; Suthanthiran, Manikkam. / In vivo hyperexpression of transforming growth factor-β1 in mice : Stimulation by cyclosporine. In: Transplantation. 1997 ; Vol. 63, No. 7. pp. 1037-1039.
@article{1f5b11be2cf141ad894860fe3e2035ed,
title = "In vivo hyperexpression of transforming growth factor-β1 in mice: Stimulation by cyclosporine",
abstract = "Background. We have demonstrated that cyclosporine (CsA) stimulates transforming growth factor (TGF) β1 expression in vitro and that growth of mammalian cells can be arrested by CsA via a TGF-β1-dependent mechanism. Herein, we have explored whether CsA stimulates TGF-β1 hyperexpression in vivo. Methods. Four groups of B6AF1 mice were studied: group 1, control; group 2, CsA pretreatment; group 3, anti-CD3 monoclonal antibody pretreatment; and group 4, CsA plus anti-CD3 pretreatment. Results. CsA pretreatment augmented TGF-β1 protein expression and increased intrarenal display of TGF-β1 mRNA. This heightened TGF-β1 expression was associated with an impaired T cell proliferative response. Conclusions. Our observations, together, advance the hypothesis that CsA might function in viva as an immunosuppressant not only by inhibiting the expression of proinflammatory cytokines (e.g., interleukin 2), but also by stimulating the expression of TGF-β1, a potent immunosuppressive cytokine. Moreover, prevention of TGF-β1 hyperexpression might prevent CsA-associated renal fibrosis, as TGF-β1 is a fibrogenic cytokine.",
author = "Ashwani Khanna and Sandip Kapur and Vijay Sharma and Baogui Li and Manikkam Suthanthiran",
year = "1997",
month = "4",
day = "15",
doi = "10.1097/00007890-199704150-00026",
language = "English",
volume = "63",
pages = "1037--1039",
journal = "Transplantation",
issn = "0041-1337",
publisher = "Lippincott Williams and Wilkins",
number = "7",

}

TY - JOUR

T1 - In vivo hyperexpression of transforming growth factor-β1 in mice

T2 - Stimulation by cyclosporine

AU - Khanna, Ashwani

AU - Kapur, Sandip

AU - Sharma, Vijay

AU - Li, Baogui

AU - Suthanthiran, Manikkam

PY - 1997/4/15

Y1 - 1997/4/15

N2 - Background. We have demonstrated that cyclosporine (CsA) stimulates transforming growth factor (TGF) β1 expression in vitro and that growth of mammalian cells can be arrested by CsA via a TGF-β1-dependent mechanism. Herein, we have explored whether CsA stimulates TGF-β1 hyperexpression in vivo. Methods. Four groups of B6AF1 mice were studied: group 1, control; group 2, CsA pretreatment; group 3, anti-CD3 monoclonal antibody pretreatment; and group 4, CsA plus anti-CD3 pretreatment. Results. CsA pretreatment augmented TGF-β1 protein expression and increased intrarenal display of TGF-β1 mRNA. This heightened TGF-β1 expression was associated with an impaired T cell proliferative response. Conclusions. Our observations, together, advance the hypothesis that CsA might function in viva as an immunosuppressant not only by inhibiting the expression of proinflammatory cytokines (e.g., interleukin 2), but also by stimulating the expression of TGF-β1, a potent immunosuppressive cytokine. Moreover, prevention of TGF-β1 hyperexpression might prevent CsA-associated renal fibrosis, as TGF-β1 is a fibrogenic cytokine.

AB - Background. We have demonstrated that cyclosporine (CsA) stimulates transforming growth factor (TGF) β1 expression in vitro and that growth of mammalian cells can be arrested by CsA via a TGF-β1-dependent mechanism. Herein, we have explored whether CsA stimulates TGF-β1 hyperexpression in vivo. Methods. Four groups of B6AF1 mice were studied: group 1, control; group 2, CsA pretreatment; group 3, anti-CD3 monoclonal antibody pretreatment; and group 4, CsA plus anti-CD3 pretreatment. Results. CsA pretreatment augmented TGF-β1 protein expression and increased intrarenal display of TGF-β1 mRNA. This heightened TGF-β1 expression was associated with an impaired T cell proliferative response. Conclusions. Our observations, together, advance the hypothesis that CsA might function in viva as an immunosuppressant not only by inhibiting the expression of proinflammatory cytokines (e.g., interleukin 2), but also by stimulating the expression of TGF-β1, a potent immunosuppressive cytokine. Moreover, prevention of TGF-β1 hyperexpression might prevent CsA-associated renal fibrosis, as TGF-β1 is a fibrogenic cytokine.

UR - http://www.scopus.com/inward/record.url?scp=0030903515&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030903515&partnerID=8YFLogxK

U2 - 10.1097/00007890-199704150-00026

DO - 10.1097/00007890-199704150-00026

M3 - Article

VL - 63

SP - 1037

EP - 1039

JO - Transplantation

JF - Transplantation

SN - 0041-1337

IS - 7

ER -