IADR Abstract Archives

Epithelial barrier breakdown by Porphyromonas gingivalis

Abstract: Porphyromonas gingivalis is one of keystone pathogens in severe and chronic manifestations of periodontal diseases. A central feature of P. gingivalis pathogenicity is dysregulation of innate immunity at the gingival epithelial interface; however, the molecular basis underlying P. gingivalis–dependent abrogation of epithelial barrier function remains unknown. Gingival epithelial cells express junctional adhesion molecule (JAM1), a tight junction–associated protein, and JAM1 homodimers regulate epithelial barrier function. We showed that Arg-specific or Lys-specific cysteine proteases (gingipains) secreted by P. gingivalis specifically degraded JAM1 at K134 and R234 in gingival epithelial cells, resulting in permeability of the gingival epithelium to 40 kDa dextran, lipopolysaccharide (LPS), and proteoglycan (PGN). A P. gingivalis strain lacking gingipains was impaired in degradation of JAM1. Next, we employed a three-dimensional (3D) multilayered tissue model using epithelial cells coated with fibronectin/gelatin nano-films. Knockdown of JAM1 in monolayer cells and 3D multilayered tissue model also increased permeability to LPS, PGN, and gingipains. Inversely, overexpression of JAM1 in epithelial cells prevented penetration by these agents following P. gingivalis infection. Our findings strongly suggest that P. gingivalis gingipains disrupt barrier function of stratified squamous epithelium via degradation of JAM1, allowing bacterial virulence factors to penetrate into subepithelial tissues. If circumstances warrant, we may be able to show the data indicating that P. gingivalis breaks through the epithelial barrier using an intercellular, rather than intracellular, pathway to get into the deeper tissues.
Japanese Division Meeting
2020 Japanese Division Meeting (Virtual)
Virtual, Japan
2020
SⅠ-4
At the front-line: Etiology of periodontitis
  • Amano, Atsuo  ( Department of Preventive Dentistry, Graduate School of Dentistry, Osaka University )
  • Takeuchi, Hiroki  ( Department of Preventive Dentistry, Graduate School of Dentistry, Osaka University )
  • Symposium I