• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of immunologyLink to Publisher's site
Immunology. Dec 1992; 77(4): 520–526.
PMCID: PMC1421646

Signal-dependent pleiotropic regulation of lymphocyte proliferation and cytokine production by 1,25-dihydroxyvitamin D3: potent modulation of the hormonal effects by phorbol esters.

Abstract

The influence of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on the proliferation of lymphocytes and on the production of interleukin-6 (IL-6), interleukin-1 beta (IL-1 beta) and interferon-gamma (IFN-gamma) was examined in normal human peripheral blood mononuclear cells (PBMC) activated in vitro either by phytohaemagglutinin (PHA) or by the monoclonal antibody to the T-cell receptor OKT3, or by the combination of each of these two stimuli with phorbol myristate acetate (PMA). 1,25(OH)2D3 inhibited the proliferative response of PBMC to PHA; this effect, however, was abrogated by the addition of PMA (1.6 nM), and it was reversed from inhibition to stimulation by higher concentrations of the phorbol ester. In contrast to the PHA-activated cells, 1,25(OH)2D3 had no effect on the proliferative response of PBMC to OKT3. Further, 1,25(OH)2D3 inhibited the release of IL-6 in cultures of PHA-activated PBMC, whereas it stimulated IL-6 with the addition of PMA in these cultures. In contrast to the PHA-activated cells, 1,25(OH)2D3 increased IL-6 release in OKT3-activated cells. IL-1 beta production was not affected in either PHA- or OKT3-activated cells by the presence of the hormone, but it was stimulated by 1,25(OH)2D3 when PMA was used as a co-stimulus with either PHA or OKT3. Finally, 1,25(OH)2D3 inhibited IFN-gamma in both PHA- and OKT3-activated cells, but these effects were attenuated in the presence of PMA. These findings demonstrate that the in vitro effects of 1,25(OH)2D3 on lymphocyte proliferation and cytokine production by PBMC are pleiotropic, and that such pleiotropism depends upon the mode of PBMC activation and presumably the signals that are generated in response to the specific agents used to activate these cells.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.1M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Tsoukas CD, Provvedini DM, Manolagas SC. 1,25-dihydroxyvitamin D3: a novel immunoregulatory hormone. Science. 1984 Jun 29;224(4656):1438–1440. [PubMed]
  • Rigby WF, Stacy T, Fanger MW. Inhibition of T lymphocyte mitogenesis by 1,25-dihydroxyvitamin D3 (calcitriol). J Clin Invest. 1984 Oct;74(4):1451–1455. [PMC free article] [PubMed]
  • Manolagas SC, Provvedini DM, Murray EJ, Tsoukas CD, Deftos LJ. The antiproliferative effect of calcitriol on human peripheral blood mononuclear cells. J Clin Endocrinol Metab. 1986 Aug;63(2):394–400. [PubMed]
  • Rigby WF, Noelle RJ, Krause K, Fanger MW. 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]
  • Tsoukas CD, Watry D, Escobar SS, Provvedini DM, Dinarello CA, Hustmyer FG, Manolagas SC. Inhibition of interleukin-1 production by 1,25-dihydroxyvitamin D3. J Clin Endocrinol Metab. 1989 Jul;69(1):127–133. [PubMed]
  • Lacey DL, Axelrod J, Chappel JC, Kahn AJ, Teitelbaum SL. Vitamin D affects proliferation of a murine T helper cell clone. J Immunol. 1987 Mar 15;138(6):1680–1686. [PubMed]
  • Hustmyer FG, Nonnecke BJ, Beitz DC, Horst RL, Reinhardt TA. 1,25-Dihydroxyvitamin D3 enhancement of concanavalin-A induced bovine lymphocyte proliferation: requirement of monocytes. Biochem Biophys Res Commun. 1988 Apr 29;152(2):545–551. [PubMed]
  • Haverty T, Haddad JG, Neilson EG. 1,25-dihydroxyvitamin D3 stimulates interleukin-2 production by a T cell lymphoma line (MLA-144) cultured in vitamin D-deficient rat serum. J Leukoc Biol. 1987 Feb;41(2):177–182. [PubMed]
  • Bhalla AK, Amento EP, Serog B, Glimcher LH. 1,25-Dihydroxyvitamin D3 inhibits antigen-induced T cell activation. J Immunol. 1984 Oct;133(4):1748–1754. [PubMed]
  • Lotz M, Jirik F, Kabouridis P, Tsoukas C, Hirano T, Kishimoto T, Carson DA. B cell stimulating factor 2/interleukin 6 is a costimulant for human thymocytes and T lymphocytes. J Exp Med. 1988 Mar 1;167(3):1253–1258. [PMC free article] [PubMed]
  • Ceuppens JL, Baroja ML, Lorre K, Van Damme J, Billiau A. Human T cell activation with phytohemagglutinin. The function of IL-6 as an accessory signal. J Immunol. 1988 Dec 1;141(11):3868–3874. [PubMed]
  • Houssiau FA, Coulie PG, Van Snick J. Distinct roles of IL-1 and IL-6 in human T cell activation. J Immunol. 1989 Oct 15;143(8):2520–2524. [PubMed]
  • Castagna M, Takai Y, Kaibuchi K, Sano K, Kikkawa U, Nishizuka Y. Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters. J Biol Chem. 1982 Jul 10;257(13):7847–7851. [PubMed]
  • Leca G, Boumsell L, Fabbi M, Reinherz EL, Kanellopoulos JM. The sheep erythrocyte receptor and both alpha and beta chains of the human T-lymphocyte antigen receptor bind the mitogenic lectin (phytohaemagglutinin) from Phaseolus vulgaris. Scand J Immunol. 1986 May;23(5):535–544. [PubMed]
  • Lorré K, Van Damme J, Verwilghen J, Baroja ML, Ceuppens JL. IL-6 is an accessory signal in the alternative CD2-mediated pathway of T cell activation. J Immunol. 1990 Jun 15;144(12):4681–4687. [PubMed]
  • Kuhweide R, Van Damme J, Lorre K, Baroja ML, Tsudo M, Ceuppens JL. Accessory cell-derived helper signals in human T-cell activation with phytohemagglutinin: induction of interleukin 2-responsiveness by interleukin 6, and production of interleukin 2 by interleukin 1 [corrected]. Cytokine. 1990 Jan;2(1):45–54. [PubMed]
  • Horii Y, Muraguchi A, Suematsu S, Matsuda T, Yoshizaki K, Hirano T, Kishimoto T. Regulation of BSF-2/IL-6 production by human mononuclear cells. Macrophage-dependent synthesis of BSF-2/IL-6 by T cells. J Immunol. 1988 Sep 1;141(5):1529–1535. [PubMed]
  • Kato K, Yokoi T, Takano N, Kanegane H, Yachie A, Miyawaki T, Taniguchi N. Detection by in situ hybridization and phenotypic characterization of cells expressing IL-6 mRNA in human stimulated blood. J Immunol. 1990 Feb 15;144(4):1317–1322. [PubMed]
  • Reichel H, Koeffler HP, Tobler A, Norman AW. 1 alpha,25-Dihydroxyvitamin D3 inhibits gamma-interferon synthesis by normal human peripheral blood lymphocytes. Proc Natl Acad Sci U S A. 1987 May;84(10):3385–3389. [PMC free article] [PubMed]
  • Yu XP, Hustmyer FG, Garvey WT, Manolagas SC. Demonstration of a 1,25-dihydroxyvitamin D3-responsive protein in human lymphocytes: immunologic crossreactivity and inverse regulation with the vitamin D receptor. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8347–8351. [PMC free article] [PubMed]

Articles from Immunology are provided here courtesy of British Society for Immunology

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Compound
    Compound
    PubChem Compound links
  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...