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

ABSTRACT: Periodontal ligament-derived mesenchymal stem cells (hPDLSCs) possess immunomodulatory abilities which are strongly enhanced by various inflammatory cytokines. Vitamin D₃ has anti-inflammatory effects on hPDLSCs and immune cells. However, no study to date has directly compared the influence of 1,25(OH)₂D₃ 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)-?, interleukin (IL)-1?, or interferon (IFN)-? in the presence of 1,25(OH)₂D₃ 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)₂D₃ on TNF-?-, IL-1?-, and IFN-?-induced gene expression of some immunomodulatory factors in hPDLSCs were compared. Under coculture conditions, 1,25(OH)₂D₃ increased or decreased CD4⁺ T lymphocyte proliferation via hPDLSCs, depending on the cytokine. hPDLSCs primed with 1,25(OH)₂D₃ and different cytokines affected pro- and anti-inflammatory cytokine expression in macrophages variably, depending on the priming cytokine. With one exception, 1,25(OH)₂D₃ significantly reduced TNF-?-, IL-1?-, and IFN-?-induced expression of all the investigated immunomediators in hPDLSCs, albeit to different extents. These results suggest that 1,25(OH)₂D₃ influences the immunomodulatory activities of hPDLSCs depending qualitatively and quantitatively on the presence of certain inflammatory cytokines.

SUBMITTER: Behm C 

PROVIDER: S-EPMC6947512 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature