Differential modulation of Toll-like receptor expression and PI3K/Akt activity in endothelial cells by LPS and glucan

Recent evidence indicates that vascular endothelial cells (EC) recognize and respond to pathogen associated molecular patterns (PAMPs) that arc present in the cell wall of pathogens or that are released into the systemic circulation during infection. During infection, EC are exposed to multiple PAMPs. However, the effect of multiple PAMPs on EC function has not been investigated. We examined the effect of bacterial LPS and/or fungal glucan on Toll-like receptor (TLR) 1, 2, 4 and 6 expression in human vascular EC. LPS or glucan stimulated TLR2 expression (23 and 46%), while LPS + glucan lowered (p<0.05) TLR2 expression. Similar changes were seen for TLR1, but TLR4 and TLR6 were not altered. We also examined the effect of LPS + glucan on activation of the phosphoinositide-3-kinase/Akt (PI3K/Akt) pathway. LPS or glucan stimulated phosphorylation of EC Akt, while the combination of LPS + glucan exerted an additive effect on EC phospho-Akt levels.