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 language | English (US) |
|---|---|
| Pages (from-to) | 718-723 |
| Number of pages | 6 |
| Journal | Transplantation |
| Volume | 60 |
| Issue number | 7 |
| State | Published - 1995 |
Fingerprint
ASJC Scopus subject areas
- Immunology
- Transplantation
Cite this
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 journal › Article
}
TY - JOUR
T1 - Regulation of transforming growth factor-β1 and its receptor by cyclosporine in human T lymphocytes
AU - Ahuja, Seema S
AU - Shrivastav, S.
AU - Danielpour, D.
AU - Balow, J. E.
AU - Boumpas, D. T.
PY - 1995
Y1 - 1995
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0028787493&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028787493&partnerID=8YFLogxK
M3 - Article
C2 - 7570983
AN - SCOPUS:0028787493
VL - 60
SP - 718
EP - 723
JO - Transplantation
JF - Transplantation
SN - 0041-1337
IS - 7
ER -