Proteolytic activity of Porphyromonas gingivalis attenuates MCP-1 mRNA expression in LPS-stimulated THP-1 cells

Abstract

Bacteria can modulate cytokine production of host cells. In this study, we examined effects of Porphyromonas gingivalis, an important periodontal pathogen, on the cytokine production in lipopolysaccharide (LPS)-stimulated THP-1 macrophagic cells. A wide range of doses of P. gingivalis increased the tumor necrosis factor-α (TNF-α) production. However, monocyte chemoattractant protein-1 (MCP-1) production was substantially suppressed by high doses of P. gingivalis and this effect was demonstrated at the mRNA level. Challenges with a congenic protease mutant strain did not significantly attenuate the MCP-1 mRNA expression and addition of leupeptin, a protease inhibitor, to the cultures largely prevented the inhibition of MCP-1 expression by P. gingivalis. Transwell experiments showed that direct contact of P. gingivalis with THP-1 cells was not required for the MCP-1 inhibition. Furthermore, blockade of internalization of P. gingivalis into THP-1 cells had no effect on the MCP-1 inhibition by P. gingivalis. Finally, degradation of MCP-1 mRNA in LPS-stimulated THP-1 cells was accelerated in the presence of P. gingivalis. These results suggest that the proteolytic activity of P. gingivalis attenuate MCP-1 mRNA expression by promoting the decay of MCP-1 mRNA in LPS-stimulated THP-1 cells.