Regulation of interleukin-1 and tumour necrosis factor gene expression in myelomonocytic cell lines by 1,25-dihydroxyvitamin D3

Abstract

1,25-dihydroxyvitamin D3[1,25-(OH)2D3] is capable of regulating cells in the immune system and affects cytokine production by both T lymphocytes and by monocytes. We examined the effects of 1,25-(OH)2D3 on the regulation of interleukin-1 beta (IL-1 beta) and tumour necrosis factor-alpha (TNF-alpha) genes in HL-60 and U937 cells. 1,25-(OH)2D3 alone only induced low level expression of the genes for these cytokines. Phorbol 12-myristate 13-acetate (PMA) strongly induced the transcription of these genes, whilst the addition of 1,25-(OH)2D3 to PMA-stimulated cells caused a further dose-dependent synergistic increase in the mRNA for both cytokines in U937 cells. In PMA-stimulated HL-60 cells, 1,25-(OH)2D3 increased the mRNA for IL-1 beta but not that for TNA-alpha, These differences may be related to the different stage of myeloid differentiation in HL-60 and U937 cells.