Upregulation of interleukin-1 beta production by 1,25-Dihydroxyvitamin D-3 in activated human macrophages

Abstract

1,25-Dihydroxyvitamin D-3 (1,25(OH)(2)D-3) plays important roles in the immune system. In contrast to its well known function in the adaptive immune system, much less is known about the immunoregulatory effects of 1,25(OH)(2)D-3 in the innate immune system, especially on activated human macrophages. Here we found that 1,25(OH)(2)D-3 strongly stimulated the production of interleukin-1 beta (IL-1 beta) in PMA-differentiated U937 cells and human monocyte-derived macrophages treated with lipopolysaccharide (LPS) or PMA. In this study, Erk1/2 appeared to mediate 1,25(OH)(2)D-3-induced expression of IL-1 beta. Parallel to the increased production of IL-1 beta, 1,25(OH)(2)D-3 increased the expression and phosphorylation of the CCAAT enhancer-binding protein beta (C/EBP beta), which is one of the key transcriptional regulatory factors for IL-1 beta transcription. These results suggest that 1,25(OH)(2)D-3 may function as a proinflammatory molecule in inflammatory macrophages.