Azithromycin recovers reductions in barrier function in human gingival epithelial cells stimulated with tumor necrosis factor-α

•Azithromycin recovered the TNF-α induced decrease of permeability in gingival epithelial cells.•The p38 MAP kinase and ERK inhibitors recovered TNF-α induced decrease of permeability.•Azithromycin inhibited the TNF-α induced phosphorylations of p38 MAP kinase and ERK.•Azithromycin recovered the TNF-α-induced reduction of E-cadherin expression.•Azithromycin inhibited the TNF-α-induced increase of IL-8 in gingival epithelial cells.

ObjectiveThe gingival epithelium plays an important role in protecting against the invasion of periodontal pathogens, and the permeability of gingival epithelial cells has been implicated in the initiation of periodontitis. Azithromycin (AZM) has been used in the treatment of chronic inflammatory airway diseases because it regulates cell–cell contact in airway epithelial cells. Therefore, AZM may also regulate barrier function in gingival epithelial cells. In the present study, we examined the effects of AZM on the permeability of human gingival epithelial cells (HGEC) under inflammatory conditions in vitro.Materials and methodsHGEC were stimulated by tumor necrosis factor-α (TNF-α) in the presence of AZM or p38 MAP kinase and ERK inhibitors. Permeability was assessed based on transepithelial electrical resistance (TER). The expression of E-cadherin, phosphorylated p38 MAP kinase, and ERK was analyzed by Western blotting.ResultsTNF-α decreased TER in HGEC, and AZM and the p38 MAP kinase and ERK inhibitors recovered this decrease. AZM inhibited the phosphorylation of ERK and p38 MAP kinase in TNF-α-stimulated HGEC. Furthermore, AZM recovered the decrease in E-cadherin expression in HGEC stimulated with TNF-α. Conclusions: These results suggested that AZM regulated gingival epithelial permeability through p38 MAP kinase and ERK signaling, and may contribute to suppress the inflammation in gingival tissue.