1. cap alpha. ,25-Dihydroxyvitamin D/sub 3/ inhibits. gamma. -interferon synthesis by normal human peripheral blood lymphocytes

Journal Article · Fri May 01 04:00:00 EDT 1987 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.84.10.3385· OSTI ID:5600355

Reichel, H; Koeffler, H P; Tobler, A; Norman, A W

1..cap alpha..,25-Dihydroxyvitamin D/sub 3/ (1,25-(OH)/sub 2/D/sub 3/), the biologically active metabolite of vitamin D/sub 3/, inhibited synthesis of ..gamma..-interferon (IFN-..gamma..) by phytohemagglutinin-activated peripheral blood lymphocytes (PBLs). A significant reduction of IFN-..gamma.. protein levels in PBL culture medium was achieved with a physiologic 1,25-(OH)/sub 2/D/sub 3/ concentration, 1,25-(OH)/sub 2/D/sub 3/ also inhibited accumulation of IFN-..gamma.. mRNA in activated PBLs in a dose-dependent fashion. The ability of 1,25-(OH)/sub 2/D/sub 3/ to modulate IFN-..gamma.. protein synthesis was unaltered in the presence of high concentrations of recombinant human interleukin 2. The suppression of IFN-..gamma.. synthesis by PBLs was specific for 1,25-(OH)/sub 2/D/sub 3/; the potencies of other vitamin D/sub 3/ metabolites were correlated with their affinities for the cellular 1,25-(OH)/sub 2/D/sub 3/ receptor. The time course of 1,25-(OH)/sub 2/D/sub 3/ receptor expression in phytohemagglutinin-activated PBLs was correlated with the time course of 1,25-(OH)/sub 2/D/sub 3/-mediated inhibition of IFN-..gamma.. synthesis. Finally, the authors examined the effects of 1,25-(OH)/sub 2/D/sub 3/ on the constitutive IFN-..gamma.. production by two human T-lymphocyte lines transformed by human T-lymphotropic virus type I. The cell lines were established from a normal donor (cell line S-LB1) and from a patient with vitamin D-dependent rickets type 2 (cell line Ab-VDR). IFN-..gamma.. synthesis by S-LB1 cells was inhibited in a dose-dependent fashion by 1,25-(OH)/sub 2/D/sub 3/, whereas IFN-..gamma.. synthesis by Ab-VDR cells was not altered by 1,25-(OH)/sub 2/D/sub 3/. The data presented in this study provide evidence for a role of 1,25-(OH)/sub 2/D/sub 3/ in immunoregulation.

• Research Organization: Univ. of California, Riverside
• OSTI ID: 5600355
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 84:10; ISSN PNASA
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
AZINES
BETA DECAY RADIOISOTOPES
BIOLOGICAL MATERIALS
BIOSYNTHESIS
BLOOD
BLOOD CELLS
BODY FLUIDS
CHOLECALCIFEROL
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
DOSE-RESPONSE RELATIONSHIPS
ELECTRON CAPTURE RADIOISOTOPES
GROWTH FACTORS
HETEROCYCLIC COMPOUNDS
INHIBITION
INTERFERON
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LABELLED COMPOUNDS
LEUKOCYTES
LYMPHOCYTES
LYMPHOKINES
MATERIALS
MESSENGER-RNA
MITOGENS
NUCLEI
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PATIENTS
PROTEINS
PYRIMIDINES
RADIOISOTOPES
RADIORECEPTOR ASSAY
RIBOSIDES
RNA
SOMATIC CELLS
SYNTHESIS
THYMIDINE
TIME DEPENDENCE
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VITAMIN D
VITAMINS