Lipopolysaccharide of P. gingivalis Induces Cyr61 Expression in HVSMC Cells

Objectives: Porphyromonas gingivalis Lipopolysaccharide (P.g. LPS) is a potent inflammatory mediator that may have important effects on the pathogenesis of atherosclerosis. Our study investigates the effect of P. g. LPS on the induction of Cyr61, a growth factor that has been linked to the development of the atherosclerotic plaque. Methods: we treat human primary vascular smooth muscle cells (hVSMC) and human monocytic cell line THP-1 with 1ug/ml P.g. LPS, and assess the expression kinetics and signaling pathway involved in Cyr61 induction by real-time PCR and western blot assays. Results: P. g. LPS can rapidly induce Cyr61 mRNA and protein expression in both hVSMCs and THP-1 cells. Using specific pharmacological inhibitors, we demonstrate that both NFkB and MAPKs signaling pathways are involved in P. g. LPS-induced Cyr61 expression in hVSMC cells. On the other hand, reactive oxygen species (ROS) along with NFkB and MAPKs signaling pathways can all mediate P. g. LPS-induced Cyr61 expression in THP-1 cells. Conclusions: Our data provide the first evidence that P. g. LPS regulates expression of Cyr61 in hVSMC and THP-1 cells. We show that P.g. LPS exert its action through the ROS, NFkB and MAPKs signaling pathways, and present evidence that this Cyr61 accumulation can be attenuated by treatment with EGCG. These data provide with future directions for improved therapeutic design in the control of periodontal related atherosclerosis.