Lipopolysaccharide of P. gingivalis Induces Egr1 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 Egr1, a master transcription factor that regulate the expression of an array of atherosclerotic genes. 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 Egr1 induction by real-time PCR and western blot assays. Results: P. g. LPS can rapidly induce Egr1 mRNA and protein expression in both hVSMCs and THP-1 cells. Using specific pharmacological inhibitors, we demonstrate that the JNK/AP-1 signaling pathway is an important mediator for P. g. LPS-induced Egr1 expression in both hVSMC and THP-1 cells. On the other hand, reactive oxygen species (ROS) NFkB and MAPKs signaling pathways have very limited contribution to the P. g. LPS-induced Egr1 expression. Conclusions: Our data provide the first evidence that P. g. LPS regulates expression of Egr1 in hVSMC and THP-1 cells. We show that P.g. LPS exert its action through the JNK/AP-1 signaling pathway, and present evidence that this Egr1 accumulation can be attenuated by treatment with curcumin. These data provide with future directions for improved therapeutic design in the control of periodontal related atherosclerosis.