Vitamin D3 Inhibits Expression of Interleukin-6 and Calcitonin Gene-Related Peptide by Transformed Dorsal Root Ganglion Neurons.

Interleukin-6 (IL-6) and the neuropeptide calcitonin gene-related peptide (CGRP) promote the generation of T helper 17 (Th17) cells. Th17-type immunity is involved in several autoimmune disorders, including psoriasis. Also, there is evidence that sensory nerves play a role in Th17-type immunity, including in psoriasis. Vitamin D (VD) blood levels vary inversely with the severity of psoriasis, and topical VD analogs are effective treatments for this disease. We have now asked whether 25-dihydroxyvitamin D3 [25(OH)D3] and the more potent, active analog 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3] inhibit IL-6 and/or α-CGRP production by transformed mouse embryonic dorsal root ganglion (DRG) neurons (MED17.11 cells), which serve as a surrogate for primary DRG neurons. After culture in differentiation medium, MED17.11 cells express markers of mature DRG neurons. Lymph nodes are innervated, so IL-6 and CGRP released from nerves are anatomically situated to influence Th17 cell generation. MED17.11 cells were cultured in differentiation medium for 48-h to induce differentiation; then, medium in each well was replaced with fresh differentiation medium containing a range of concentrations of 25(OH)D3 or 1α,25(OH)2D3. Twenty-four and 48-h later, supernatants were collected, and cells were harvested and lysed. IL-6 and α-CGRP content of supernatants and lysates were assessed by ELISA. Both 25(OH)D3 and 1α,25(OH)2D3 significantly inhibited IL-6 content of supernatants and α-CGRP content of cell lysates in a dose-dependent manner with 1α,25(OH)2D3 being more potent. 25(OH)D3 and 1α,25(OH)2D3 also inhibited expression of IL-6 mRNA. VD may beneficially affect disorders involving Th17-type immunity by decreasing expression of IL-6 and α-CGRP by DRG nerves.