Epithelial Cell Sensing and Responses to P. gingivalis

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DESCRIPTION: (provided by applicant) P. gingivalis, a gram (-) anaerobe, has been recognized widely as the predominant pathogenic organism in adult periodontitis. P. gingivalis successfully colonizes the hard and soft tissues of the mouth (teeth and mucosa) and can invade and replicate in human gingival epithelial cells. Fimbriae are a major adherence-mediating determinant of P. gingivalis and also participate in the invasion process. The overall objectives of this study are the identification of the gingival epithelial cell receptor(s) for P. gingivalis fimbriae, and the determination of the epithelial cell downstream signaling events induced by P. gingivalis fimbriae-receptor binding. Our preliminary work has identified integrins as potential epithelial cell receptors for P. gingivalis fimbriae. The role of integrins as the cognate receptor for P. gingivalis fmbriae and in the subsequent signal transduction events will be main subject of this proposal. Fimbriae-receptor interactions will be investigated by antibody and peptide inhibition assays, electron microscopy and anti-sense RNA technology. The events that occur downstream of fimbriae-receptor binding will be examined by studying potentially interacting cell signaling and structural proteins. The tyrosine phosphorylation and trans- and colocalization of these proteins will be investigated by immunoprecipitation, fluorescence microscopy, and microinjection techniques. We expect this study will provide novel and crucial insights into understanding of the pathogenesis of periodontal diseases and also help advance the current treatment regimes designed to prevent or delay the disease process.