1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] inhibited the secretion of γ-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 γ-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 γ-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.
This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture and by a grant for cancer research from the Ministry of Health and Welfare of Japan.