Grant: Project Grant

A large segment of the adult population suffers from periodontal diseases (PDs) that can result in loss of teeth, a financial burden, and potentially contribute to many systemic conditions. The pathogenesis of PDs is a complex process in which intricate subgingival bacterial biofilm induces inflammation that leads to tissue degradation and bone loss. In health, junctional epithelium (JE) links the gingiva to the tooth enamel, creating a seal and preventing bacteria from entering the gingival tissue. In PD, bone loss develops around the teeth with periodontal pockets and the JE transforms into pocket epithelium (PE). However, it is not clear how JE/PE participates in the regulation of periodontal inflammation. In the inflammatory infiltrate, the outcome of the cytokine response is regulated by the production of pro-inflammatory cytokines that are countered by anti-inflammatory cytokines. These cytokines need to be activated for biological function. An integrin known as alpha-v-beta-6 can activate them. Mutations in this integrin cause PD in mice and humans. We have shown that JE constitutively expresses this integrin and these anti-inflammatory cytokines. In PD, the expression of this integrin in PE is strongly downregulated, resulting in "acquired integrin deficiency." This integrin-mediated cytokine activation in JE appears to be crucial for the maintenance of periodontal health and preventing systemic inflammation. The factors leading to the downregulation of this integrin expression in PE cells are not known. In the present proposal, we will determine the mechanisms through which this integrin expression is downregulated in JE/PE in periodontal disease and how this integrin "deficiency" regulates cytokine expression in epithelial cells. The long-term goal is to determine the molecular mechanism of periodontal inflammation and use this information for preventive therapies.