Micronutrient modulation of NF-κB in oral keratinocytes exposed to periodontal bacteria.
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-κB 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 α-lipoic acid was able to abrogate bacterially-induced pro-inflammatory changes in the H400 oral epithelial cell line. Initial studies indicated that α-lipoic acid supplementation (1-4 mM) significantly reduced cell attachment; lower concentrations (<0.5 mM) enabled >85% cell adhesion at 24 h. While a pro-inflammatory response, demonstrable by NF-κB translocation, gene expression and protein production was evident in H400 cells following exposure to P. gingivalis and F. nucleatum, pre-incubation of cells with 0.5 mM α-lipoic acid modulated this response. α-Lipoic acid pre-treatment significantly decreased levels of bacterially-induced NF-κB activation and IL-8 protein production, and differentially modulated transcript levels for IL-8, IL-1β, TNF-α and GM-CSF, TLR2, 4, 9, S100A8, S100A9, lysyl oxidase, NF-κB1, HMOX, and SOD2. Overall, the data indicate that α-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.
School of Dentistry, College of Medical & Dental Sciences, University of Birmingham, UK. M.R.Milward@bham.ac.uk
Michael R
MR
Milward
Iain Lc
IL
Chapple
Kevin
K
Carter
John B
JB
Matthews
Paul R
PR
Cooper
D016866:Bacteroidaceae Infections / Q000188:drug therapy / Q000276:immunology*; D002460:Cell Line; D005674:Fusobacterium Infections / Q000188:drug therapy / Q000276:immunology*; D016967:Fusobacterium nucleatum / Q000276:immunology*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D009055:Mouth / Q000276:immunology / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism*; D016966:Porphyromonas gingivalis / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D008063:Thioctic Acid / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects / Q000276:immunology
D018836:Inflammation Mediators; D016209:Interleukin-8; D016328:NF-kappa B; D014157:Transcription Factors; D008063:Thioctic Acid