Immuno-modulatory effects of vitamin D3 in human monocyte and macrophages

Vitamin D3 [1a,25-(OH)2D3], involved in the regulation of body calcium homeostasis, promotes immature myeloid precursor cells differentiation into monocytes/macrophages. In this study we compared the regulatory interaction between 1a,25-(OH)2D3 and tumor necrosis factor (TNF)-a or lipopolysaccharide (LPS) in the mRNA expression of interleukin (IL)-1b, (IL)-6, TNF-a, toll like receptors (TLR)-2 and (TLR)-4 in freshly isolated human monocyte (MonoT0) and in macrophages cultured for seven days (MØT7). Additionally, we detected the effect of 1a,25-(OH)2D3 on macrophages chemotaxis. The expression of IL-1b, IL-6 and TNF-a, as well as TLR-2 and TLR-4 in MonoT0 and in MØT7 was examined by real time RT-PCR. Macrophages chemotaxis was analyzed by using horizontal chemotaxis agarose spot assay. We found that 1a,25-(OH)2D3 influences macrophages chemotaxis and differently modulates the expression of IL-1b, IL-6, TNF-a and TLRs in the two different stages of monocytes/macrophage maturation. In conclusion our data add new information about the role of 1a,25-(OH)2D3 on the expression of inflammatory mediators in human monocyte/macrophages, underlying the complex function of these cells. Investigating the differences in the pattern of expression of immune-mediators produced by MonoT0 and MØT7 may provide a new way to examine their biochemical and molecular function and may constitute a model system with well-defined behavior with respect to early or tardive events in the innate immune response.