Interaction among vitamin D3 analogue KH 1060, TNF-α, and vitamin D receptor protein in peripheral blood mononuclear cells of inflammatory bowel disease patients

BackgroundThe active form of vitamin D, 1,25(OH)2D3, exerts important effects on proliferation and differentiation of many cell types, and immunoregulatory activities in particular on T cell-mediated immunity.AimThe aim of this study was to investigate whether KH 1060, a vitamin D analogue, could decrease tumor necrosis factor-alpha (TNF-α) levels in patients with inflammatory bowel disease (IBD).MethodsPBMC proliferation was determined by [3H]thymidine incorporation. TNF-α levels were measured by ELISA kit; VDR, Bcl-2 and Bax protein levels with Western blot analysis.ResultsKH 1060 inhibited PBMC proliferation and decreased TNF-α levels in IBD patients and this effect was synergistic with anti-TNF-α. VDR protein levels were significantly increased by PBMC treatment with KH 1060 or anti-TNF-α or their combination in ulcerative colitis (UC) patients, and decreased in Crohn's disease (CD) patients, treating the cells with KH 1060. In UC patients an increase in Bcl-2 and Bax levels was observed incubating, PBMC with KH 1060 or anti-TNF-α or their combination. In CD patients a slight decrease in Bcl-2 levels was registered when anti-TNF alone or in association with KH 1060 was used. Bax protein levels were slightly increased in the presence of KH 1060 alone or in combination with anti-TNF.ConclusionThis study shows that KH 1060 acts as an immunomodulator on PBMC, acting as TNF-α inhibitor. This finding provides strong evidence that vitamin D status could be an important regulator of immunity IBD.