Lipopolysaccharide (LPS) is a key inflammatory mediator. Due to its ability
to potently activate host inflammatory and innate defense responses, it ha
s been proposed to function as an important molecule that alerts the host o
f potential bacterial infection. However, although highly conserved, LPS co
ntains important structural differences among different bacterial species t
hat can significantly alter host responses. For example, LPS obtained from
Porphyromonas gingivalis: an etiologic agent for periodontitis; causes a hi
ghly unusual host innate host response. II is an agonist for human monocyte
s and an antagonist for human endothelial cells. Correspondingly, although
it activates p38 MAP kinase in human monocytes, P. gingivalis LPS does not
activate p38 nor ERK MAP kinase in endothelial cells. In Fact, P. gingivali
s LPS is an effective inhibitor of Escherichia coli LPS induced p38 phospho
rylation. These data show that P. gingivalis LPS modulates host defenses in
endothelial cells by interfering with MAP kinase activation. In addition,
P. gingivalis LPS is unusual in that it engages TLR-2 but not TLR-4 when ex
amined in stably transfected CHO cell lines. We propose that, since LPS is
a key ligand for the human innate host defense system, these unusual proper
ties of P. gingivalis LPS are associated with the bacterium's role in the p
athogenesis of periodontitis.