Vitamin D3 Modulates Inflammatory and Antimicrobial Responses in Oral Epithelial Cells Exposed to Periodontitis-Associated Bacteria

The oral epithelium is essential for maintaining oral health and plays a key role in the onset and progression of periodontitis. It serves as both a mechanical and immunological barrier and possesses antimicrobial activity. Vitamin D₃, a hormone with known immunomodulatory functions, may influence oral epithelial responses. This study investigated the effects of two vitamin D₃ metabolites on key immunological and antimicrobial functions of oral epithelial cells, both under basal conditions and during bacterial challenge. Ca9-22 oral epithelial cells were treated with 1,25(OH)₂D₃ or 25(OH)D₃ in the presence or absence of <i>Tannerella forsythia</i>, <i>Fusobacterium nucleatum</i>, or <i>Porphyromonas gingivalis</i>. Inflammatory responses were assessed by measuring gene and protein expression of IL-1β and IL-8. Antimicrobial activity was evaluated via expression of LL-37, hBD-2, and hBD-3, as well as direct bacterial killing assays. Expression of epithelial integrity markers E-cadherin and ICAM-1 was also analyzed. Vitamin D₃ metabolites reduced IL-8 expression and significantly increased LL-37 expression and production in Ca9-22 cells. Both forms enhanced antimicrobial activity against all tested pathogens and modulated epithelial integrity markers. Vitamin D₃ positively regulates antimicrobial and barrier functions in oral epithelial cells, suggesting a potential role in supporting oral health and preventing periodontitis progression.