Toll-Like Receptor 4-Mediated Hyper-Responsiveness of Gingival Epithelial Cells to Lipopolysaccharide in High-Glucose Environments

Background: Increasing evidence indicates that diabetes mellitus increases the incidence and severity of periodontitis. Toll-like receptors (TLRs) play a role in the pathogenic processes of diabetes and its complications, but the effect of high glucose on TLRs in patients with diabetes and periodontitis is still unclear. Methods: Two kinds of diabetes rat models were established. Human gingival epithelial cells (HGECs) were established and challenged with Porphyromonas gingivalis lipopolysaccharide (LPS) in the context of high glucose in vitro. The expressions of TLR2 and TLR4 were detected using immunohistochemistry, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and flow cytometry. The TLR4 inhibitor ethyl (6R)-6-[(2-chloro-4-fluorophenyl) sulfamoyl]cyclohexene-1-carboxylate (TAK-242) was applied to block the TLR4 in HGECs, and the inflammatory factors were detected by qRT-PCR. Results: The expression of TLR2 and TLR4 in gingival tissue from both rat diabetes models was significantly increased compared with that of healthy controls. Moreover, TLR4 expression was also markedly increased in HGECs incubated with high glucose. The expression of interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1 were significantly increased in HGECs while challenged with LPS in the context of high glucose; however, the expression inflammatory cytokines were decreased significantly, whereas TLR4 was blocked by TAK-242. Conclusion: High glucose contributes to an upregulated expression of TLR4 in gingival epithelium, and TLR4-dependent inflammatory response may promote the susceptibility to periodontitis in patients with diabetes.