Milward, Michael Robert (2010)
Ph.D. thesis, University of Birmingham.
Restricted to Repository staff only until 31 July 2014.
Pocket/sulcular epithelium is the first line of defence to plaque bacteria and its potential role in periodontitis is investigated. This thesis describes the development of a model system, utilising an immortal epithelial cell line (H400) in order to investigate responses to periodontal pathogen stimulation (P. gingivalis and F. nucleatum) in terms of NF-\(\kappa\)B activation, differential gene expression and cytokine production. The pathogenesis of periodontitis suggests that susceptible patients exhibit a hyper-inflammatory response to plaque bacteria, so an attempt to modulate the pro-inflammatory epithelial response using a natural di-thiol antioxidant \(\alpha\)-lipoate was also investigated. Data demonstrated that periodontal pathogens P. gingivalis and F. nucleatum elicited a pro-inflammatory response in the H400 model system. This was confirmed by demonstrating NF-\(\kappa\)B activation, gene expression changes and downstream cytokine production. Ontological grouping of gene expression changes revealed a range of gene functions which support the hypothesis that the epithelium may play a role in the initiation and propagation of the periodontal lesion. In addition, alipoate was able to modulate this inflammatory response but not completely block this essential defence mechanism. Data obtained indicates the potential of utilising \(\alpha\)-lipoate as an adjunct in the management of periodontitis.
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