TLR4 mediates LPS-induced VEGF expression in odontoblasts.
Lipopolysaccharide (LPS) from gram-negative bacteria cell walls such as Prevotella intermedia and Escherichia coli induce vascular endothelial growth factor (VEGF) expression in odontoblasts, but not in undifferentiated dental pulp cells. CD14 and TLR4 are responsible for LPS signaling in macrophages, but their expression levels and function in dental pulp cells are unknown. We showed here that murine odontoblast-like cells (MDPC-23) express CD14 and TLR4 by immunohistochemistry and flow cytometry. In contrast, undifferentiated dental pulp cells (OD-21) presented low or no expression of these two receptors. MDPC-23 cells showed CD14 and TLR4 up-regulation upon exposure to LPS, as determined by real time PCR. Dominant negative murine TLR4 (DN-mTLR4) transfected MDPC-23 cells did not show upregulated VEGF expression in response to LPS stimulation. These results demonstrate that odontoblast-like cells express CD14 and TLR4, and that LPS-induced VEGF expression is mediated, at least in part, by TLR4 signaling.
Botero
Tatiana M
TM
Department of Cariology, Restorative Sciences and Endodontics, University of Michigan, School of Dentistry, Ann Arbor, Michigan 48109-1078, USA.
Shelburne
Charles E
CE
Holland
G Rex
GR
Hanks
Carl T
CT
Nör
Jacques E
JE
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D003782:Dental Pulp / Q000166:cytology; D004926:Escherichia coli; D005347:Fibroblasts / Q000502:physiology; D005434:Flow Cytometry; D005881:Gingiva / Q000166:cytology; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000166:cytology; D018950:Lipopolysaccharide Receptors / Q000032:analysis / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000502:physiology; D051379:Mice; D009804:Odontoblasts / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000032:analysis / Q000502:physiology*; D014162:Transfection; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000502:physiology*
D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D051197:Toll-Like Receptor 4; D042461:Vascular Endothelial Growth Factor A