1,25(OH)2D3 Differently Affects Immunomodulatory Activities of Mesenchymal Stem Cells Depending on the Presence of TNF-α, IL-1β and IFN-γ

Periodontal ligament-derived mesenchymal stem cells (hPDLSCs) possess immunomodulatory abilities which are strongly enhanced by various inflammatory cytokines. Vitamin D-3 has anti-inflammatory effects on hPDLSCs and immune cells. However, no study to date has directly compared the influence of 1,25(OH)(2)D-3 on the immunomodulatory activities of hPDLSCs in the presence of different cytokines. In the present study, the effects of hPDLSCs treated with tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, or interferon (IFN)-gamma in the presence of 1,25(OH)(2)D-3 on the proliferation of allogenic CD4(+) T lymphocyte or on the functional status of primary CD68(+) macrophages were analyzed in coculture models. Additionally, the effects of 1,25(OH)(2)D-3 on TNF-alpha-, IL-1 beta-, and IFN-gamma-induced gene expression of some immunomodulatory factors in hPDLSCs were compared. Under coculture conditions, 1,25(OH)(2)D-3 increased or decreased CD4(+) T lymphocyte proliferation via hPDLSCs, depending on the cytokine. hPDLSCs primed with 1,25(OH)(2)D-3 and different cytokines affected pro- and anti-inflammatory cytokine expression in macrophages variably, depending on the priming cytokine. With one exception, 1,25(OH)(2)D-3 significantly reduced TNF-alpha-, IL-1 beta-, and IFN-gamma-induced expression of all the investigated immunomediators in hPDLSCs, albeit to different extents. These results suggest that 1,25(OH)(2)D-3 influences the immunomodulatory activities of hPDLSCs depending qualitatively and quantitatively on the presence of certain inflammatory cytokines.