Upregulation of interleukin-1β production by 1,25-Dihydroxyvitamin D₃ in activated human macrophages

1,25-Dihydroxyvitamin D₃ (1,25(OH)₂D₃) 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)₂D₃ in the innate immune system, especially on activated human macrophages. Here we found that 1,25(OH)₂D₃ strongly stimulated the production of interleukin-1β (IL-1β) 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)₂D₃-induced expression of IL-1β. Parallel to the increased production of IL-1β, 1,25(OH)₂D₃ increased the expression and phosphorylation of the CCAAT enhancer-binding protein β (C/EBPβ), which is one of the key transcriptional regulatory factors for IL-1β transcription. These results suggest that 1,25(OH)₂D₃ may function as a proinflammatory molecule in inflammatory macrophages.