Abstract
Chronic periodontal diseases are characterised by a dysregulated and exaggerated inflammatory/immune response to plaque bacteria. We have demonstrated previously that oral keratinocytes up-regulate key molecular markers of inflammation, including NF-kappa B and cytokine signalling, when exposed to the periodontal bacteria Porphyromonas gingivalis and Fusobacterium nucleatum in vitro. The purpose of the current study was to investigate whether alpha-lipoic acid was able to abrogate bacterially-induced pro-inflammatory changes in the H400 oral epithelial cell line. Initial studies indicated that alpha-lipoic acid supplementation (1-4mM) significantly reduced cell attachment; lower concentrations (<0.5mM) enabled >85% cell adhesion at 24 h. While a pro-inflammatory response, demonstrable by NF-kappa B translocation, gene expression and protein production was evident in H400 cells following exposure to P. gingivalis and F. nucleatum, pre-incubation of cells with 0.5mM alpha-lipoic acid modulated this response. alpha-Lipoic acid pre-treatment significantly decreased levels of bacterially-induced NF-kappa B activation and IL-8 protein production, and differentially modulated transcript levels for IL-8, IL-1 beta, TNF-alpha and GM-CSF, TLR2, 4, 9, S100A8, S100A9, lysyl oxidase, NF-kappa B-1, HMOX, and SOD2. Overall, the data indicate that alpha-lipoic acid exerts an anti-inflammatory effect on oral epithelial cells exposed to periodontal bacteria and thus may provide a novel adjunctive treatment for periodontal diseases.