Signaling by Toll-like receptor 2 and 4 agonists results in differential gene expression in murine macrophages

Lipopolysaccharide (LPS) derived from the periodontal pathogen Porphyromona s gingivalis has been reported to differ structurally and functionally from enterobacterial LPS. These studies demonstrate that in contrast to protein -free enterobacterial LPS, a similarly purified preparation of P. gingivali s LPS exhibited potent Toll-like receptor 2 (TLR2), rather than TLR4, agoni st activity to elicit gene expression and cytokine secretion in murine macr ophages and transfectants, More importantly, TLR2 stimulation by this P. gi ngivalis LPS preparation resulted in differential expression of a panel of genes that are normally induced in murine macrophages by Escherichia coli L PS. These data suggest that (i) P. gingivalis LPS does not signal through T LR4 and (ii) signaling through TLR2 and through TLR4 differs quantitatively and qualitatively, Our data support the hypothesis that the shared signali ng pathways elicited by TLR2 and by TLR4 agonists must diverge in order to account for the distinct patterns of inflammatory gene expression.