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. 1991 Dec;74(4):589–593.

1,25(OH)2D3 regulates c-myc mRNA levels in tonsillar T lymphocytes.

R Karmali 1, M Hewison 1, N Rayment 1, S M Farrow 1, A Brennan 1, D R Katz 1, J L O'Riordan 1
PMCID: PMC1384765  PMID: 1783418

Abstract

The effects of 1,25(OH)2D3 on proliferation, c-myc mRNA levels and 1,25(OH)2D3 receptor expression in activated tonsillar T lymphocytes were studied. Activation of resting T cells with phytohaemagglutinin (PHA) for 72 hr led to an increase in proliferation, c-myc mRNA levels and to induction of 1,25(OH)2D3 receptor expression. However, when activation was carried out in the presence of 1,25(OH)2D3, there was inhibition of PHA-stimulated proliferation and c-myc mRNA levels. Increased cell proliferation, c-myc mRNA expression and 1,25(OH)2D3 receptor number were also observed, albeit to a lesser extent, when T cells were stimulated by phorbol myristate acetate (PMA), anti-CD3 antibody or A23187. However, in these cases 1,25(OH)2D3 was unable to prevent increased proliferation or c-myc mRNA expression. PMA and anti-CD3 used in combination produced similar or greater changes in proliferation, c-myc mRNA levels, 1,25(OH)2D3 receptor expression and responsiveness to the hormone when compared to PHA alone. Thus the inhibition of c-myc expression in activated T lymphocytes by 1,25(OH)2D3 can be related to its anti-proliferative effects. Moreover this inhibition seems to be dependent on the level of 1,25(OH)2D3 receptor expression, which in turn appears to be related to the degree of cell activation.

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Selected References

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  1. Abraham R. T., Ho S. N., Barna T. J., McKean D. J. Transmembrane signaling during interleukin 1-dependent T cell activation. Interactions of signal 1- and signal 2-type mediators with the phosphoinositide-dependent signal transduction mechanism. J Biol Chem. 1987 Feb 25;262(6):2719–2728. [PubMed] [Google Scholar]
  2. Bhalla A. K., Amento E. P., Clemens T. L., Holick M. F., Krane S. M. Specific high-affinity receptors for 1,25-dihydroxyvitamin D3 in human peripheral blood mononuclear cells: presence in monocytes and induction in T lymphocytes following activation. J Clin Endocrinol Metab. 1983 Dec;57(6):1308–1310. doi: 10.1210/jcem-57-6-1308. [DOI] [PubMed] [Google Scholar]
  3. Crabtree G. R. Contingent genetic regulatory events in T lymphocyte activation. Science. 1989 Jan 20;243(4889):355–361. doi: 10.1126/science.2783497. [DOI] [PubMed] [Google Scholar]
  4. Dalla-Favera R., Gelmann E. P., Martinotti S., Franchini G., Papas T. S., Gallo R. C., Wong-Staal F. Cloning and characterization of different human sequences related to the onc gene (v-myc) of avian myelocytomatosis virus (MC29). Proc Natl Acad Sci U S A. 1982 Nov;79(21):6497–6501. doi: 10.1073/pnas.79.21.6497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dobbs J. F., Katz D. R. Human T-cell activation: comparative studies on the role of different phorbol esters. Immunology. 1988 Jan;63(1):133–137. [PMC free article] [PubMed] [Google Scholar]
  6. Dong Y., Cairns W., Okret S., Gustafsson J. A. A glucocorticoid-resistant rat hepatoma cell variant contains functional glucocorticoid receptor. J Biol Chem. 1990 May 5;265(13):7526–7531. [PubMed] [Google Scholar]
  7. Gardner P. Calcium and T lymphocyte activation. Cell. 1989 Oct 6;59(1):15–20. doi: 10.1016/0092-8674(89)90865-9. [DOI] [PubMed] [Google Scholar]
  8. Heikkila R., Schwab G., Wickstrom E., Loke S. L., Pluznik D. H., Watt R., Neckers L. M. A c-myc antisense oligodeoxynucleotide inhibits entry into S phase but not progress from G0 to G1. 1987 Jul 30-Aug 5Nature. 328(6129):445–449. doi: 10.1038/328445a0. [DOI] [PubMed] [Google Scholar]
  9. Hewison M., Barker S., Brennan A., Katz D. R., O'Riordan J. L. Modulation of myelomonocytic U937 cells by vitamin D metabolites. Bone Miner. 1989 Mar;5(3):323–333. doi: 10.1016/0169-6009(89)90010-x. [DOI] [PubMed] [Google Scholar]
  10. Iho S., Takahashi T., Kura F., Sugiyama H., Hoshino T. The effect of 1,25-dihydroxyvitamin D3 on in vitro immunoglobulin production in human B cells. J Immunol. 1986 Jun 15;136(12):4427–4431. [PubMed] [Google Scholar]
  11. Karmali R., Bhalla A. K., Farrow S. M., Williams M. M., Lal S., Lydyard P. M., O'Riordan J. L. Early regulation of c-myc mRNA by 1,25-dihydroxyvitamin D3 in human myelomonocytic U937 cells. J Mol Endocrinol. 1989 Jul;3(1):43–48. doi: 10.1677/jme.0.0030043. [DOI] [PubMed] [Google Scholar]
  12. Karmali R., Farrow S., Hewison M., Barker S., O'Riordan J. L. Effects of 1,25-dihydroxyvitamin D3 and cortisol on bovine and human parathyroid cells. J Endocrinol. 1989 Oct;123(1):137–142. doi: 10.1677/joe.0.1230137. [DOI] [PubMed] [Google Scholar]
  13. Koeffler H. P., Bishop J. E., Reichel H., Singer F., Nagler A., Tobler A., Walka M., Norman A. W. Lymphocyte cell lines from vitamin D-dependent rickets type II show functional defects in the 1 alpha,25-dihydroxyvitamin D3 receptor. Mol Cell Endocrinol. 1990 Mar 26;70(1):1–11. doi: 10.1016/0303-7207(90)90053-b. [DOI] [PubMed] [Google Scholar]
  14. Lemire J. M., Adams J. S., Sakai R., Jordan S. C. 1 alpha,25-dihydroxyvitamin D3 suppresses proliferation and immunoglobulin production by normal human peripheral blood mononuclear cells. J Clin Invest. 1984 Aug;74(2):657–661. doi: 10.1172/JCI111465. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Manolagas S. C., Deftos L. J. The vitamin D endocrine system and the hematolymphopoietic tissue. Ann Intern Med. 1984 Jan;100(1):144–146. doi: 10.7326/0003-4819-100-1-144. [DOI] [PubMed] [Google Scholar]
  16. Manolagas S. C., Provvedini D. M., Murray E. J., Murray S. S., Tsonis P. A., Spandidos D. A. Association between the expression of the c-myc oncogene mRNA and the expression of the receptor protein for 1,25-dihydroxyvitamin D3. Proc Natl Acad Sci U S A. 1987 Feb;84(3):856–860. doi: 10.1073/pnas.84.3.856. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Matsumoto K., Hashimoto K., Nishida Y., Hashiro M., Yoshikawa K. Growth-inhibitory effects of 1,25-dihydroxyvitamin D3 on normal human keratinocytes cultured in serum-free medium. Biochem Biophys Res Commun. 1990 Jan 30;166(2):916–923. doi: 10.1016/0006-291x(90)90898-w. [DOI] [PubMed] [Google Scholar]
  18. Nunn J. D., Katz D. R., Barker S., Fraher L. J., Hewison M., Hendy G. N., O'Riordan J. L. Regulation of human tonsillar T-cell proliferation by the active metabolite of vitamin D3. Immunology. 1986 Dec;59(4):479–484. [PMC free article] [PubMed] [Google Scholar]
  19. Reed J. C., Nowell P. C., Hoover R. G. Regulation of c-myc mRNA levels in normal human lymphocytes by modulators of cell proliferation. Proc Natl Acad Sci U S A. 1985 Jun;82(12):4221–4224. doi: 10.1073/pnas.82.12.4221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Reitsma P. H., Rothberg P. G., Astrin S. M., Trial J., Bar-Shavit Z., Hall A., Teitelbaum S. L., Kahn A. J. Regulation of myc gene expression in HL-60 leukaemia cells by a vitamin D metabolite. Nature. 1983 Dec 1;306(5942):492–494. doi: 10.1038/306492a0. [DOI] [PubMed] [Google Scholar]
  21. Rigby W. F., Denome S., Fanger M. W. Regulation of lymphokine production and human T lymphocyte activation by 1,25-dihydroxyvitamin D3. Specific inhibition at the level of messenger RNA. J Clin Invest. 1987 Jun;79(6):1659–1664. doi: 10.1172/JCI113004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Rigby W. F., Noelle R. J., Krause K., Fanger M. W. The effects of 1,25-dihydroxyvitamin D3 on human T lymphocyte activation and proliferation: a cell cycle analysis. J Immunol. 1985 Oct;135(4):2279–2286. [PubMed] [Google Scholar]
  23. Rigby W. F., Stacy T., Fanger M. W. Inhibition of T lymphocyte mitogenesis by 1,25-dihydroxyvitamin D3 (calcitriol). J Clin Invest. 1984 Oct;74(4):1451–1455. doi: 10.1172/JCI111557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Rigby W. F. The immunobiology of vitamin D. Immunol Today. 1988 Feb;9(2):54–58. [PubMed] [Google Scholar]
  25. Rook G. A., Steele J., Fraher L., Barker S., Karmali R., O'Riordan J., Stanford J. Vitamin D3, gamma interferon, and control of proliferation of Mycobacterium tuberculosis by human monocytes. Immunology. 1986 Jan;57(1):159–163. [PMC free article] [PubMed] [Google Scholar]
  26. Smeland E., Godal T., Ruud E., Beiske K., Funderud S., Clark E. A., Pfeifer-Ohlsson S., Ohlsson R. The specific induction of myc protooncogene expression in normal human B cells is not a sufficient event for acquisition of competence to proliferate. Proc Natl Acad Sci U S A. 1985 Sep;82(18):6255–6259. doi: 10.1073/pnas.82.18.6255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Tsoukas C. D., Provvedini D. M., Manolagas S. C. 1,25-dihydroxyvitamin D3: a novel immunoregulatory hormone. Science. 1984 Jun 29;224(4656):1438–1440. doi: 10.1126/science.6427926. [DOI] [PubMed] [Google Scholar]

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