Abstract

Objective: An important property of vitamin D is its ability to induce the antimicrobial peptide, LL-37, a human cathelicidin. LL-37 also promotes innate immunity, reduces levels of pro-inflammatory cytokines, and stimulates proliferation and migration of epithelial cells. Despite its beneficial effects, vitamin D can cause hypercalcemia. In this study, effects of vitamin D and a non-calcemic vitamin D analog on gingival epithelial cell proliferation and LL-37 production, and in an in vitro wound healing model, were determined.

Methods: Human gingival epithelial cells were exposed to vitamin D [1,25(OH)2 D3] or an analog [20(OH)D3]. Effects on cell viability (activity of a mitochondrial enzyme), proliferation (incorporation of BrdU into DNA) and LL-37 production (by ELISA) were determined, and effects on wound healing were evaluated in vitro via a “scrape” wound healing model. Data were analyzed using ANOVA and Scheffe’s F procedure for post hoc comparisons.

Results: Vitamin D and the analog had no significant effect on viability, and both increased LL-37 production. Vitamin D, but not the analog, increased proliferation (~50% increase; p<0.03). Neutralizing anti-LL-37 did not significantly alter proliferation. Vitamin D and the analog significantly increased the rate of in vitro wound closure, which was not affected by the presence of the neutralizing LL- 37 antibody, indicating other mechanisms besides LL-37 were responsible for the increase rate of wound closure.

Conclusion: While vitamin D and the vitamin D analog increased production of LL-37 20-30%, the increased rates of in vitro wound closure caused by vitamin D and the analog, and stimulation of cell proliferation by vitamin D, probably occur through mechanisms other than LL-37 production.