Regulatory effect of 17β-estradiol on the expression of β-defensin-2 and proinflammatory cytokines in human oral epithelial cells.

Background: Although estrogen deficiency has been proposed as a risk factor for oral mucosal inflammatory diseases in post-menopausal women, the mechanisms involved remain unclear. This study aimed to investigate the effect of 17β-estradiol (E2) on the inflammatory response stimulated by interleukin-1 beta (IL-1β) in human oral mucosal epithelial cells (hOMECs) and its possible mechanism.

Methods: Primary hOMECs were obtained from female infants and cultured in keratinocyte growth medium. The hOMECs at second passage were collected and stimulated by 10  mol/L ICI182,780 or 10  mol/L G1 for 1 hour, E2 (10  mol/L, 10  mol/L, 10  mol/L) for 36 hour, 100 ng/mL IL-1β for 12 hours, respectively. Human beta-2 defensin (hBD-2), tumor necrosis factor-alpha (TNF)-α, IL-6, IL-8, estrogen receptor-alpha (ERα), estrogen receptor-beta (ERβ), and G protein-coupled receptor 30 (GPR30) mRNA levels and protein levels were measured by real-time quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), and Western Blot (WB), respectively.

Results: Expression of hBD-2 and inflammatory cytokines increased after IL-1β stimulation, which was down-regulated by E2 pre-treatment. With ICI182,780, the suppression of E2 on hBD-2 mRNA was attenuated. With G1, the mRNA expression and protein expression of hBD-2 were reduced.

Conclusion: Pre-treatment of hOMECs with E2 at physiological concentrations inhibited the IL-1β-induced expression of hBD-2 and inflammatory cytokines. The protective effects of E2 suggest its potential use treating oral inflammatory diseases in clinical practice.