Expression of various Toll-like receptors, NOD1, and NOD2, in human oral epithelial cells, and their function

Abstract

Oral epithelium is endowed with innate immune receptors for bacterial components, which play important roles in host defense against bacterial infection. We examined the expression of various Toll-like receptors (TLRs), NOD1 and NOD2 in oral epithelial cells, and the production of β-defensin 2 and peptidoglycan recognition proteins (PGRPs) upon stimulation with their respective chemically synthesized ligands. We found a clear expression of TLR4 as well as TLR2, and a strong expression of NOD1 and NOD2 in normal oral epithelial tissues by immunohistochemical analysis. In the inflamed oral epithelium, cell-surface localizations of TLR2 and TLR4 were more clearly observed than in the healthy tissue. We also showed that oral epithelial cells in culture constitutively expressed TLR3 and TLR7 in addition to TLR2, TLR4, NOD1, and NOD2, and stimulation with synthetic ligands for these receptors (TLR2 agonistic lipopeptide, TLR3 agonistic poly I:C, TLR4 agonistic lipid A, TLR7 agonistic single-stranded RNA, NOD1 agonistic iE-DAP and NOD2 agonistic muramyldipeptide) markedly up-regulated the expression of antibacterial factors, such as β-defensin 2 and PGRPs, but not the proinflammatory cytokines. These findings indicate that these molecules in oral epithelial cells are functional receptors that induce antibacterial responses without excessive inflammatory responses.