P. gingivalis Modulates RAGE Expression in GEC Cells

Objectives: The receptor for advanced glycation end product RAGE is a multiligand tissue receptor expressed in many cells including gingival epithelial and fibroblast cells. Signaling of RAGE results in inflammatory response including activation of some NF-kappa B pathways. Overexpression of RAGE was demonstrated in gingival tissue of patients with type 2 diabetes with periodontal disease. RAGE was also upregulated in gingival tissue incubated with nornicotine, a smoking by product. The purpose of the present study was to examine the hypothesis that P. gingivalis, a major pathogen in periodontal disease, can modify the expression of RAGE in primary cultures of human gingival epithelial cells. Methods: Gingival epithelial cells (GEC) were incubated with and without P. gingivalis (100 MOI) for 30min, 2h, 4h, 16h and 24 h. The cells were then assayed for mRNA for RAGE by RT-PCR and protein production by western blots. Results: P. gingivalis induced decreased expression of mRAGE in GEC resulting in 34% expression compared to control after 4h, 67% after 16h and 86% after 24h. The protein production was decreased compared to control for 4-16h and eventually recovered after 24h to a level higher than control. Conclusions: P. gingivalis may attenuate the inflammatory response of the host cell by transient down regulation of the proinflammatory receptor RAGE. Supported by NIH U24 DE 16509 and DE11111.