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.
- 1,25-Dihydroxyvitamin D