Mechanisms of Porphyromonas gingivalis-induced monocyte chemoattractant protein-1 expression in endothelial cells

Monocyte chemoattractant protein-1 (MCP-1) is expressed in vascular endothelial cells of inflamed gingival tissues and plays an important role in periodontal pathogenesis. Endothelial cells produce high levels of MCP-1 in response to Porphyromonas gingivalis, an important periodontal pathogen. The present study investigated the mechanisms involved in MCP-1 production by human umbilical vein endothelial cells (HUVEC) following infection with P. gingivalis. In contrast to P. gingivalis, Bacteroides forsythus only weakly stimulated MCP-1 production while Treponema denticola could not induce MCP-1 in HUVEC. The MCP-1 production was independent of endogenous interleukin (IL)-1 alpha as IL-1 receptor antagonist treatment did not reduce MCP-1 production by P. gingivalis. Meanwhile, antioxidant treatment and inhibition of NAD(P)H oxidase significantly reduced MCP-1 production. Pharmacological inhibition of p38 mitogen-associated protein (MAP) kinase, c-Jun N-terminal kinase (INK), nuclear factor-kappa B (NF-kappa B) or activator protein-1 (AP-1) also substantially attenuated P. gingivalis-induced MCP-1 expression by HUVEC. Indeed, activation of NF-kappa B and AP-1 was observed in P. gingivalis-infected HUVEC. These results suggest that MCP-1 expression is upregulated in P. gingivalis-infected endothelial cells via reactive oxygen species, p38 MAP kinase, JNK, NF-kappa B, and AP-1. (c) 2004 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved.