Abstract
Periodontal diseases manifest by the formation of deep pockets between the gingiva and teeth where multispecies bacterial biofilms flourish, causing inflammation and bone loss. Epithelial cell receptor αvβ6 integrin that regulates inflammation by activating the anti-inflammatory cytokine transforming growth factor-β1, is highly expressed in healthy junctional epithelium that connects the gingiva to the tooth enamel. However, its expression is attenuated in human periodontal disease. Moreover, Itgb6−/− mice display increased periodontal inflammation compared to wild-type mice. We hypothesized that bacterial biofilms present in the periodontal pockets suppress αvβ6 integrin levels in periodontal disease and that this change aggravates inflammation. To this end, we generated three-week-old multi-species oral biofilms in vitro and treated cultured gingival epithelial cells (GECs) with their extracts. The biofilm extracts caused suppression of β6 integrin expression and upregulation of pro-inflammatory cytokines, including interleukin-1β and -6. Furthermore, GECs with β6 integrin siRNA knockdown showed increased interleukin-1β expression, indicating that αvβ6 integrin-deficiency is associated with pro-inflammatory cytokine responsiveness. FSL-1, a synthetic bacterial lipopeptide, also suppressed β6 integrin expression in GECs. Therefore, biofilm components, including lipopeptides, may downregulate αvβ6 integrin expression in the pocket epithelium and thus promote epithelial cell-driven pro-inflammatory response in periodontal disease.
Highlights
About half of the adult population of the United States suffers from periodontal diseases, in which bacterial biofilm induces gingival inflammation, leading to tissue degradation, alveolar bone loss around teeth and even tooth loss[1]
We have previously shown that the expression of β1 and β4 integrins is variable in human periodontal disease, showing areas of focal loss and areas of increased expression[28]
ITGB6 expression could be suppressed in gingival epithelial cells (GECs) by blocking Transforming growth factor-β1 (TGF-β1) signaling with an inhibitor of TGF-β receptor kinase activity (SB431542)
Summary
About half of the adult population of the United States suffers from periodontal diseases, in which bacterial biofilm induces gingival inflammation, leading to tissue degradation, alveolar bone loss around teeth and even tooth loss[1]. In vitro studies investigating the response of the gingival epithelial cells (GECs) to dental plaque microorganisms have shown that these cells respond to most subgingival bacterial species by increasing their pro-inflammatory cytokine expression[5,6,7]. These cytokines include, but are not limited to, interleukin-1β (IL-1β) and IL-6. Integrin αvβ[6] is a cell surface receptor for the TGF-β1 and -β3 latency-associated peptides, and a key activator of these cytokines in epithelial cells[13]
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