Background: Porphyromonas gingivalis lipopolysaccharide (LPS) is a crucial virulence factor strongly associated with chronic periodontitis which is the primary cause of tooth loss in adults. It exhibits remarkable heterogeneity containing tetra-(LPS(1435/1449)) and penta-(LPS(1690)) acylated lipid A structures. Human gingival fibroblasts (HGFs) as the main resident cells of human gingiva play a key role in regulating matrix metalloproteinases (MMPs) and contribute to periodontal homeostasis. This study investigated the expression and regulation of MMPs1-3 and tissue inhibitors of MMP-1 (TIMP-1) in HGFs in response to P. gingivalis LPS(1435/1449) and LPS(1690) and hexa-acylated E. coli LPS as a reference. The expression of MMPs 1-3 and TIMP-1 was evaluated by real-time PCR and ELISA.
Results: The MMP-3 mRNA and protein were highly upregulated in P. gingivalis LPS(1690)- and E. coli LPS-treated cells, whereas no induction was observed in P. gingivalis LPS(1435/1449)-treated cells. On the contrary, the expression of MMP-1 and -2 was not significantly affected by P. gingivalis LPS lipid A heterogeneity. The TIMP-1 mRNA was upregulated in P. gingivalis LPS(1435/1449)- and E. coli LPS-treated cells. Next, signal transduction pathways involved in P. gingivalis LPS-induced expression of MMP-3 were examined by blocking assays. Blockage of p38 MAPK and ERK significantly inhibited P. gingivalis LPS(1690)-induced MMP-3 expression in HGFs.
Conclusion: The present findings suggest that the heterogeneous lipid A structures of P. gingivalis LPS differentially modulate the expression of MMP-3 in HGFs, which may play a role in periodontal pathogenesis.