PorphyromonasgingivalisLipopolysaccharide AntagonizesEscherichiacoliLipopolysaccharide at Toll-Like Receptor 4 in HumanEndothelialCells

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Abstract
E. colilipopolysaccharide (LPS) induces cytokine and adhesion molecule expression via the toll-like receptor 4 (TLR4) signaling complex in human endothelial cells. In the present study, we investigated the mechanism by whichPorphyromonas gingivalisLPS antagonizesE. coliLPS-dependent activation of human endothelial cells.P. gingivalisLPS at 1 μg/ml inhibited bothE. coliLPS (10 ng/ml) andMycobacterium tuberculosisheat shock protein (HSP) 60.1 (10 μg/ml) stimulation of E-selectin mRNA expression in human umbilical vein endothelial cells (HUVEC) without inhibiting interleukin-1 beta (IL-1β) stimulation.P. gingivalisLPS (1μ g/ml) also blocked bothE. coliLPS-dependent andM. tuberculosisHSP60.1-dependent but not IL-1β-dependent activation of NF-κB in human microvascular endothelial (HMEC-1) cells, consistent with antagonism occurring upstream from the TLR/IL-1 receptor adaptor protein, MyD88. Surprisingly,P. gingivalisLPS weakly but significantly activated NF-κB in HMEC-1 cells in the absence ofE. coliLPS, and theP. gingivalisLPS-dependent agonism was blocked by transient expression of a dominant negative murine TLR4. Pretreatment of HUVECs withP. gingivalisLPS did not influence the ability ofE. coliLPS to stimulate E-selectin mRNA expression. Taken together, these data provide the first evidence thatP. gingivalisLPS-dependent antagonism ofE. coliLPS in human endothelial cells likely involves the ability ofP. gingivalisLPS to directly compete withE. coliLPS at the TLR4 signaling complex.