Estrogen prevented gingival barrier injury from <i>Porphyromonas gingivalis</i> lipopolysaccharide

The postmenopausal population usually suffers from more severe periodontal disease than non-menopausal women due to the decrease and low levels of estrogen, especially β-estradiol (E2). While additional estrogen therapy can effectively relieve alveolar bone resorption, this suggests that estrogen has played an important role in the development of periodontitis. The integrity of the gingival epithelial barrier plays a key role in protecting gingival tissue from inflammatory injury caused by pathogens. However, it remains unclear whether estrogen can maintain the integrity of the gingival epithelial barrier to reduce inflammatory injury. Here, using an infection model established with <i>Porphyromonas gingivalis</i> lipopolysaccharide (LPS) in human gingival epithelial cells (hGECs) and ovariectomized or Sham mice, we assessed the protective effect of estrogen on the gingival barrier using qPCR, western blotting, immunohistochemistry, and transcriptome analysis. The results showed that estrogen restored epithelial barrier function to inhibit <i>P. gingivalis</i>-LPS invasion and further downregulate the inflammatory reaction (<i>P</i> < 0.05) by upregulating expressions of tight junction proteins (such as JAM1 and OCLN) at mRNA and protein levels in both hGECs and ovariectomized or Sham mice (<i>P</i> < 0.05). Estrogen also protected against alveolar bone resorption and preserved barrier integrity in both ovariectomized and Sham mice (<i>P</i> < 0.05). In conclusion, E2 prevented the progression of gingival epithelial barrier damage and inflammation induced by <i>P. gingivalis</i>-LPS by increasing the expression of tight junction proteins. The protective effect of estrogen on gingival epithelial barrier injury highlighted its potential application in treating periodontitis and inflammatory diseases involving epithelial barrier dysfunction.