Signaling by toll-like receptor 2 and 4 agonists results in differential gene expression in murine macrophages.
Lipopolysaccharide (LPS) derived from the periodontal pathogen Porphyromonas 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. gingivalis LPS exhibited potent Toll-like receptor 2 (TLR2), rather than TLR4, agonist activity to elicit gene expression and cytokine secretion in murine macrophages and transfectants. More importantly, TLR2 stimulation by this P. gingivalis LPS preparation resulted in differential expression of a panel of genes that are normally induced in murine macrophages by Escherichia coli LPS. These data suggest that (i) P. gingivalis LPS does not signal through TLR4 and (ii) signaling through TLR2 and through TLR4 differs quantitatively and qualitatively. Our data support the hypothesis that the shared signaling pathways elicited by TLR2 and by TLR4 agonists must diverge in order to account for the distinct patterns of inflammatory gene expression.
Hirschfeld
M
M
Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah, USA.
Weis
J J
JJ
Toshchakov
V
V
Salkowski
C A
CA
Cody
M J
MJ
Ward
D C
DC
Qureshi
N
N
Michalek
S M
SM
Vogel
S N
SN
D000818:Animals; D029721:Drosophila Proteins; D004926:Escherichia coli / Q000276:immunology; D015870:Gene Expression; D018664:Interleukin-12 / Q000096:biosynthesis; D008050:Lipid A / Q000737:chemistry; D008070:Lipopolysaccharides / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000819:agonists*; D051379:Mice; D008809:Mice, Inbred C3H; D010510:Periodontal Diseases / Q000382:microbiology; D016966:Porphyromonas gingivalis / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000819:agonists*; D015398:Signal Transduction; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D029721:Drosophila Proteins; D008050:Lipid A; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12