Enhanced interleukin-1 production by human monocyte cell lines following treatment with 5-azacytidine.

Recent studies suggest that DNA modification, such as methylation of specific bases or substitution of altered bases, can play an important role in the control of eukaryotic gene expression. We chose to examine the effects of two DNA modifying agents, 5-azacytidine (AZA) and 5-bromodeoxyuridine (BUdR), on interleukin-1 (IL-1) gene expression in the human monocyte cell lines THP-1 and U937.1. THP-1 produced IL-1 upon stimulation with lipopolysaccharide (LPS), whereas U937.1 did not. Following treatment with AZA, U937.1 cells could be induced to produce IL-1 beta mRNA and release IL-1, but only if a stimulus such as LPS was present. In addition, the level of IL-1 beta mRNA produced and IL-1 released by THP-1 cells after induction could be doubled by treatment with AZA. In contrast, we were unable to alter IL-1 production by treatment of cells with BUdR in the absence or presence of inducers. These results suggest that the production of IL-1 may be, in part, regulated by methylation of DNA.