1,25-Dihydroxyvitamin D3-regulated expression of genes involved in human T-lymphocyte proliferation and differentiation.
1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] inhibited the secretion of gamma-interferon from human T-lymphocytes activated by the calcium ionophore, A23187, or phytohemagglutinin with or without 12-O-tetradecanoylphorbol-13-acetate. The agent also inhibited cell proliferation and interleukin 2 secretion by these cells. The inhibition of gamma-interferon secretion was time and dose dependent and partially abolished by the addition of exogenous human recombinant interleukin 2. To elucidate the molecular events by which 1,25-(OH)2D3 inhibits cell proliferation and lymphokine secretion, complementary DNA probes were used to follow the expression of genes involved in human T-lymphocyte proliferation and differentiation. 1,25-(OH)2D3 inhibited the expression of interleukin 2 and gamma-interferon messenger RNA in human lymphocytes activated by phytohemagglutinin and 12-O-tetradecanoylphorbol-13-acetate. It also inhibited the accumulation of c-myc protooncogene messenger RNA and, to a lesser extent, interleukin 2 receptor messenger RNA in these cells. However, it did not affect the expression of the HLA-DR gene. These results suggest that 1,25-(OH)2D3 selectively regulates T-lymphocyte activation-related genes at the level of messenger RNA.
D000001:Calcimycin / Q000494:pharmacology; D002117:Calcitriol / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D007376:Interleukin-2 / Q000235:genetics; D008213:Lymphocyte Activation / Q000187:drug effects; D008222:Lymphokines / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics; D011971:Receptors, Immunologic / Q000235:genetics; D015375:Receptors, Interleukin-2; D012636:Secretory Rate / Q000187:drug effects; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004268:DNA-Binding Proteins; D007376:Interleukin-2; D008222:Lymphokines; D011518:Proto-Oncogene Proteins; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D000001:Calcimycin; D007371:Interferon-gamma; D002117:Calcitriol; D013755:Tetradecanoylphorbol Acetate