Regulation of transforming growth factor-β1 and its receptor by cyclosporine in human T lymphocytes

Seema S Ahuja, S. Shrivastav, D. Danielpour, J. E. Balow, D. T. Boumpas

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

Scarring, fibrosis, and immunosuppression occurs with chronic cyclosporine (CsA) administration. We postulated that CsA may induce transforming growth factor (TGF)-β1 secretion from human T lymphocytes, a cytokine with immunoregulatory effects that has been implicated in the pathogenesis of wound healing and scarring. TGF-β1 was measured in serum-free supernatants harvested from T lymphocytes stimulated in the presence of CsA by a specific sandwich ELISA. CsA (10-1000 ng/ml) enhanced TGF-β1 secretion by approximately 40-80% in a dose-dependent manner. Increased TGF-β1 secretion in the presence of CsA was accompanied by a 2- to 4-fold increase in TGF- β1 mRNA levels due to both enhancement of its nuclear transcription as well as prolongation of TGF-β1 mRNA half-life. To determine whether the increase in TGF-β1 secretion was also accompanied by a concomitant change in its receptor, TGF-β1 receptor expression was analyzed by cross-linking of radioiodinated TGF-β1. Unactivated T lymphocytes expressed both a 105-kDa and a 65-kDa TGF-β receptor. Upon stimulation, a transient increase in receptor density was seen at 12 hr, followed by a decline at later time points. Cells treated with CsA exhibited at least 2-fold higher levels of TGF-β receptors in a dose-dependent manner. Thus, CsA enhances the production of TGF-β1 protein as well as the expression of its receptor in activated T lymphocytes. Enhanced TGF-β1 production and binding may contribute to the immunosuppressive and fibrosis-promoting effects of CsA therapy.

Original languageEnglish (US)
Pages (from-to)718-723
Number of pages6
JournalTransplantation
Volume60
Issue number7
StatePublished - 1995

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Transforming Growth Factors
Cyclosporine
T-Lymphocytes
Growth Factor Receptors
Cicatrix
Fibrosis
Messenger RNA
Immunosuppressive Agents
Wound Healing
Immunosuppression
Half-Life
Enzyme-Linked Immunosorbent Assay

ASJC Scopus subject areas

  • Immunology
  • Transplantation

Cite this

Ahuja, S. S., Shrivastav, S., Danielpour, D., Balow, J. E., & Boumpas, D. T. (1995). Regulation of transforming growth factor-β1 and its receptor by cyclosporine in human T lymphocytes. Transplantation, 60(7), 718-723.

Regulation of transforming growth factor-β1 and its receptor by cyclosporine in human T lymphocytes. / Ahuja, Seema S; Shrivastav, S.; Danielpour, D.; Balow, J. E.; Boumpas, D. T.

In: Transplantation, Vol. 60, No. 7, 1995, p. 718-723.

Research output: Contribution to journalArticle

Ahuja, SS, Shrivastav, S, Danielpour, D, Balow, JE & Boumpas, DT 1995, 'Regulation of transforming growth factor-β1 and its receptor by cyclosporine in human T lymphocytes', Transplantation, vol. 60, no. 7, pp. 718-723.
Ahuja, Seema S ; Shrivastav, S. ; Danielpour, D. ; Balow, J. E. ; Boumpas, D. T. / Regulation of transforming growth factor-β1 and its receptor by cyclosporine in human T lymphocytes. In: Transplantation. 1995 ; Vol. 60, No. 7. pp. 718-723.
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