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Signal-dependent pleiotropic regulation of lymphocyte proliferation and cytokine production by 1,25-dihydroxyvitamin D3: potent modulation of the hormonal effects by phorbol esters.
Immunology 1992; 77(4):520-6I

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.

Authors+Show Affiliations

Section of Endocrinology and Metabolism, VA Medical Center, Indianapolis, Indiana 46202.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

1493924

Citation

Hustmyer, F G., et al. "Signal-dependent Pleiotropic Regulation of Lymphocyte Proliferation and Cytokine Production By 1,25-dihydroxyvitamin D3: Potent Modulation of the Hormonal Effects By Phorbol Esters." Immunology, vol. 77, no. 4, 1992, pp. 520-6.
Hustmyer FG, Girasole G, Manolagas SC. Signal-dependent pleiotropic regulation of lymphocyte proliferation and cytokine production by 1,25-dihydroxyvitamin D3: potent modulation of the hormonal effects by phorbol esters. Immunology. 1992;77(4):520-6.
Hustmyer, F. G., Girasole, G., & Manolagas, S. C. (1992). Signal-dependent pleiotropic regulation of lymphocyte proliferation and cytokine production by 1,25-dihydroxyvitamin D3: potent modulation of the hormonal effects by phorbol esters. Immunology, 77(4), pp. 520-6.
Hustmyer FG, Girasole G, Manolagas SC. Signal-dependent Pleiotropic Regulation of Lymphocyte Proliferation and Cytokine Production By 1,25-dihydroxyvitamin D3: Potent Modulation of the Hormonal Effects By Phorbol Esters. Immunology. 1992;77(4):520-6. PubMed PMID: 1493924.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Signal-dependent pleiotropic regulation of lymphocyte proliferation and cytokine production by 1,25-dihydroxyvitamin D3: potent modulation of the hormonal effects by phorbol esters. AU - Hustmyer,F G, AU - Girasole,G, AU - Manolagas,S C, PY - 1992/12/1/pubmed PY - 1992/12/1/medline PY - 1992/12/1/entrez SP - 520 EP - 6 JF - Immunology JO - Immunology VL - 77 IS - 4 N2 - 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. SN - 0019-2805 UR - https://www.unboundmedicine.com/medline/citation/1493924/Signal_dependent_pleiotropic_regulation_of_lymphocyte_proliferation_and_cytokine_production_by_125_dihydroxyvitamin_D3:_potent_modulation_of_the_hormonal_effects_by_phorbol_esters_ L2 - https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/1493924/ DB - PRIME DP - Unbound Medicine ER -