Suppression of ?v?6 Integrin Expression by Polymicrobial Oral Biofilms in Gingival Epithelial Cells.

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 ?v?6 integrin that regulates inflammation by activating the anti-inflammatory cytokine transforming growth factor-?1, 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 ?v?6 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 ?6 integrin expression and upregulation of pro-inflammatory cytokines, including interleukin-1? and -6. Furthermore, GECs with ?6 integrin siRNA knockdown showed increased interleukin-1? expression, indicating that ?v?6 integrin-deficiency is associated with pro-inflammatory cytokine responsiveness. FSL-1, a synthetic bacterial lipopeptide, also suppressed ?6 integrin expression in GECs. Therefore, biofilm components, including lipopeptides, may downregulate ?v?6 integrin expression in the pocket epithelium and thus promote epithelial cell-driven pro-inflammatory response in periodontal disease.

SUBMITTER: Bi J 

PROVIDER: S-EPMC5493688 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature