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. 1991 Aug;85(2):326–330. doi: 10.1111/j.1365-2249.1991.tb05727.x

Interleukin-2 receptor gene expression in kidney transplant recipients treated with cyclosporin A.

N Yoshimura 1, T Oka 1, T Amagai 1, Y Horii 1, J Imanishi 1
PMCID: PMC1535752  PMID: 1864013

Abstract

We examined the effects of cyclosporin A (CsA) administered in vivo on the capacity of peripheral blood mononuclear cells (PBMC) from kidney transplant recipients to express IL-2 receptor (IL-2R) gene at the level of mRNA after mitogen stimulation in vitro. There were no differences in the percentage of IL-2R+ cells among the groups of normal individuals, azathioprine-prednisolone treated, and CsA-prednisolone-treated recipients, using FITC-labelled monoclonal anti-IL-2R antibody (anti-alpha chain): 40.3 +/- 10.1% and 62.8 +/- 11.1% of normal PBMC (n = 18), 37.0 +/- 9.3% and 61.7 +/- 5.8% of PBMC from azathioprine-prednisolone-treated recipients (n = 20), and 37.7 +/- 9.6% and 60.7 +/- 12.7% of PBMC from CsA-prednisolone-treated recipients (n = 20) expressed IL-2R after 24 h and 48 h of phytohaemagglutinin stimulation, respectively. However, in a study of Northern blotting using cDNA for IL-2R (anti-alpha chain specific), both the 3500 and 1400 bp families of IL-2R mRNA were remarkably decreased in PBMC from CsA-prednisolone-treated recipients compared with azathioprine-prednisolone-treated recipients and normal individuals. These studies demonstrated that CsA could inhibit IL-2R gene expression at the level of mRNA at physiological concentration.

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Selected References

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  1. Abbud-Filho M., Kupiec-Weglinski J. W., Araujo J. L., Heidecke C. D., Tilney N. L., Strom T. B. Cyclosporine therapy of rat heart allograft recipients and release of interleukins (IL 1, IL 2, IL 3): a role for IL 3 in graft tolerance? J Immunol. 1984 Nov;133(5):2582–2586. [PubMed] [Google Scholar]
  2. Bettens F., Walker C., Bonnard G. D., de Weck A. L. Effect of cyclosporin A on the early activation of human T helper lymphocytes: inhibition of RNA-synthesis and modification of the expression of activation antigens. Immunobiology. 1985 Dec;170(5):434–447. doi: 10.1016/S0171-2985(85)80067-X. [DOI] [PubMed] [Google Scholar]
  3. Depper J. M., Leonard W. J., Drogula C., Krönke M., Waldmann T. A., Greene W. C. Interleukin 2 (IL-2) augments transcription of the IL-2 receptor gene. Proc Natl Acad Sci U S A. 1985 Jun;82(12):4230–4234. doi: 10.1073/pnas.82.12.4230. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Grabstein K., Dower S., Gillis S., Urdal D., Larsen A. Expression of interleukin 2, interferon-gamma, and the IL 2 receptor by human peripheral blood lymphocytes. J Immunol. 1986 Jun 15;136(12):4503–4508. [PubMed] [Google Scholar]
  5. Granelli-Piperno A., Andrus L., Steinman R. M. Lymphokine and nonlymphokine mRNA levels in stimulated human T cells. Kinetics, mitogen requirements, and effects of cyclosporin A. J Exp Med. 1986 Apr 1;163(4):922–937. doi: 10.1084/jem.163.4.922. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Granelli-Piperno A. Lymphokine gene expression in vivo is inhibited by cyclosporin A. J Exp Med. 1990 Feb 1;171(2):533–544. doi: 10.1084/jem.171.2.533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hatakeyama M., Minamoto S., Uchiyama T., Hardy R. R., Yamada G., Taniguchi T. Reconstitution of functional receptor for human interleukin-2 in mouse cells. Nature. 1985 Dec 5;318(6045):467–470. doi: 10.1038/318467a0. [DOI] [PubMed] [Google Scholar]
  8. Hess A. D., Tutschka P. J., Santos G. W. Effect of cyclosporin A on human lymphocyte responses in vitro. III. CsA inhibits the production of T lymphocyte growth factors in secondary mixed lymphocyte responses but does not inhibit the response of primed lymphocytes to TCGF. J Immunol. 1982 Jan;128(1):355–359. [PubMed] [Google Scholar]
  9. Kahan B. D., Van Buren C. T., Lin S. N., Ono Y., Agostino G., LeGrue S. J., Boileau M., Payne W. D., Kerman R. H. Immunopharmacological monitoring of cyclosporin A-treated recipients of cadaveric kidney allografts. Transplantation. 1982 Jul;34(1):36–45. doi: 10.1097/00007890-198207000-00007. [DOI] [PubMed] [Google Scholar]
  10. Leonard W. J., Krönke M., Peffer N. J., Depper J. M., Greene W. C. Interleukin 2 receptor gene expression in normal human T lymphocytes. Proc Natl Acad Sci U S A. 1985 Sep;82(18):6281–6285. doi: 10.1073/pnas.82.18.6281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Miyawaki T., Yachie A., Ohzeki S., Nagaoki T., Taniguchi N. Cyclosporin A does not prevent expression of Tac antigen, a probable TCGF receptor molecule, on mitogen-stimulated human T cells. J Immunol. 1983 Jun;130(6):2737–2742. [PubMed] [Google Scholar]
  12. Nikaido T., Shimizu A., Ishida N., Sabe H., Teshigawara K., Maeda M., Uchiyama T., Yodoi J., Honjo T. Molecular cloning of cDNA encoding human interleukin-2 receptor. Nature. 1984 Oct 18;311(5987):631–635. doi: 10.1038/311631a0. [DOI] [PubMed] [Google Scholar]
  13. Orosz C. G., Roopenian D. C., Widmer M. B., Bach F. H. Analysis of cloned T cell function. II. Differential blockade of various cloned T cell functions by cyclosporine. Transplantation. 1983 Dec;36(6):706–711. doi: 10.1097/00007890-198336060-00024. [DOI] [PubMed] [Google Scholar]
  14. Reed J. C., Abidi A. H., Alpers J. D., Hoover R. G., Robb R. J., Nowell P. C. Effect of cyclosporin A and dexamethasone on interleukin 2 receptor gene expression. J Immunol. 1986 Jul 1;137(1):150–154. [PubMed] [Google Scholar]
  15. Starzl T. E., Klintmalm G. B., Weil R., 3rd, Porter K. A., Iwatsuki S., Schroter G. P., Fernandez-Bueno C., MacHugh N. Cyclosporin A and steroid therapy in sixty-six cadaver kidney recipients. Surg Gynecol Obstet. 1981 Oct;153(4):486–494. [PMC free article] [PubMed] [Google Scholar]
  16. Stubbs S. S. Corticosteroids and bioavailability. Transplant Proc. 1975 Mar;7(1):11–19. [PubMed] [Google Scholar]
  17. Taniguchi T., Pang R. H., Yip Y. K., Henriksen D., Vilcek J. Partial characterization of gamma (immune) interferon mRNA extracted from human lymphocytes. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3469–3472. doi: 10.1073/pnas.78.6.3469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Teshigawara K., Wang H. M., Kato K., Smith K. A. Interleukin 2 high-affinity receptor expression requires two distinct binding proteins. J Exp Med. 1987 Jan 1;165(1):223–238. doi: 10.1084/jem.165.1.223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Yoshimura N., Kahan B. D. Pharmacodynamic assessment of the in vivo cyclosporine effect on interleukin-2 production by lymphocytes in kidney transplant recipients. Transplantation. 1985 Dec;40(6):661–666. doi: 10.1097/00007890-198512000-00018. [DOI] [PubMed] [Google Scholar]
  20. Yoshimura N., Oka T., Clark S. C., Kahan B. D. The inhibition of interleukin 2 (IL-2) gene expression at the level of messenger RNA by in vivo cyclosporine treatment in kidney transplant recipients. Transplant Proc. 1987 Aug;19(4):3510–3512. [PubMed] [Google Scholar]
  21. Yoshimura N., Oka T., Kita M., Teraoka H., Hirai Y. Combination therapy of cyclosporine with steroid inhibits gamma-interferon and interleukin-1 gene expression at the level of mRNA synthesis in vivo. J Clin Immunol. 1989 Jul;9(4):322–328. doi: 10.1007/BF00918664. [DOI] [PubMed] [Google Scholar]

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