A Nonsecosteroidal Vitamin D Receptor Modulator Ameliorates Experimental Autoimmune Encephalomyelitis without Causing Hypercalcemia
Figure 9
VDR ligands modulate peptide-specific recall responses from MOG-immunized mice. (a) Compound A inhibits the proliferation of MOG-specific splenocytes. Splenocytes from groups () of MOG-immunized mice were harvested at day 28 and analyzed ex vivo for proliferative responses to MOG at the concentrations indicated. Cells were cultured in triplicate in 96-well plates for 60 hours, and proliferation was measured by 3H-thymidine incorporation during the final 8 hours of culture. Values represent the mean ± SE of triplicate for each peptide concentration. Ovalbumin (OVA) peptide was used as specificity control since the mice were immunized with MOG peptide. Vehicle group consisted of MOG immunized mice treated with vehicle (sesame seed oil). CFA group was mock immunized with CFA only (without MOG peptide) and was not treated with any ligands. (b) Effect of VDR ligands on cytokine elaboration in MOG-immunized animals. For dendritic cell IL-10 production, CD11c+ cells were purified on day 28 from splenocytes obtained from MOG-immunized animals. The effect of VDR ligands on IL-10 levels from splenic CD11c+ cultures stimulated for 24 hours with 100 ng/mL LPS is shown. VDR ligands decreased IFN-γ elaboration from splenocyte cultures stimulated for 48 hours with 80 μg/mL MOG peptide. IL-10 and IFN-γ protein levels were measured by ELISA.
