Porphyromonas gingivalis and its lipopolysaccharide differentially regulate the expression of cathepsin B in endothelial cells

Abstract

Porphyromonas gingivalis infection and cathepsins protease upregulation are independently implicated in atherosclerosis worsening. In this study, we evaluated the effects of P. gingivalis infection and P. gingivalis -purified lipopolysaccharide (Pg-LPS) stimulation on the expression of cathepsin B (CATB) in endothelial cells (ECs). Analysis of the enzymatic activity and expression of CATB were investigated at the messenger RNA, protein and protein-phosphorylation levels. Effects of Toll-like receptors 2 and 4 blocking on CATB activity were also analysed. Our results showed that P. gingivalis and Pg-LPS significantly increased the activity of CATB but with different kinetics. The peak of CATB activity was observed 3 h after P. gingivalis infection but it appeared 48 h after Pg-LPS stimulation. The increase of CATB activity was related to its rapid tyrosine-dephosphorylation during P. gingivalis infection, whereas the levels of CATB messenger RNAs and proteins did not vary after P. gingivalis infection or Pg-LPS stimulation. Inhibition of Toll-like-receptors 2 and 4 differentially decreased P. gingivalis and Pg-LPS CATB activations. These results showed for the first time that P. gingivalis infection rapidly affects ECs and modulates CATB activity, whereas Pg-LPS effects appear to be delayed. This study suggests that direct infection of ECs by P. gingivalis may worsen atherosclerotic plaque formation via activation of the CATB pathway.