Endothelial and gingival epithelial cells challenged with Porphyromonas gingivalis lipolysaccharides

Objective: mounting evidence has accumulated supporting a role for periodontal pathogens including P.gingivalis as a potential risk factor for several systemic diseases such as atherosclerosis. The aim of our in vitro study was to challenge both endothelial and human gingival epithelial cell (hGEC) cultures with P.gingivalis 1 µg/ml LPS and to compare the induced innate immune responses. Methods: the mRNA expression of different molecules involved either in the sensing of pathogens-associated molecular patterns (TLR4, MD2, CD14, MyD88, TRIF) or in the inflammatory response (PPAR-γ, PAR-2, IL-8 and TNF-α) has been evaluated by RT-PCR and Southern blot. Results: we have shown an up-regulation of the expression of messengers of the TLR4 signal transduction pathway through adapter molecules MyD88 and TRIF in both HUVEC and hGEC. The activation of the TLR4 pathway led to the expression of the pro-inflammatory cytokines IL-8 in both HUVEC and hGEC and TNF-α in hGEC only. Interestingly, the PPAR-γ messenger, a nuclear receptor responding to LPS, was up-regulated in both cell types, although only transiently in HUVEC. PAR-2 mRNA was predominantly up-regulated in HUVEC compared to hGEC. This receptor is involved in the thrombus formation in sclerotic arteries, but is also the target of P. gingivalis gingipains in the periodontal pocket. Conclusion: the potent pro-inflammatory response elicited by P.gingivalis in endothelial cells could participate in the establishment of the early events involved in the development of atherosclerosis.