Peptidoglycan recognition proteins (PGRPs), a novel family of pattern recognition molecules involved in innate immunity conserved from insects to mammals, recognize bacterial cell wall peptidoglycan (PGN) and have been suggested to act as anti-bacterial factors. In humans, four kinds of PGRPs (PGRP-L, -Iα, -Iβ and -S) have been cloned and all four of them bind PGN. Chemically synthesized pathogen-associated molecular patterns (PAMPs) in bacterial cell surface components (synthetic lipopeptide [TLR2 agonist], synthetic lipid A [TLR4 agonist], synthetic iE-DAP [NOD1 agonist], and muramyldipeptide [MDP, NOD2 agonist]) markedly upregulated the mRNA expressions of the four PGRPs and cell surface expressions of PGRP-Iα and -Iβ, but did not induce either mRNA expression or the secretion of inflammatory cytokines in oral epithelial cells. Suppression of the expressions of TLR2, TLR4, NOD1 and NOD2 by RNA interference specifically inhibited the upregulation of PGRP mRNA expression induced by lipopeptide, lipid A, iE-DAP and MDP, respectively. In addition, these PAMPs definitely activated nuclear factor (NF)-κB in the epithelial cells, and suppression of NF-κB activation clearly prevented the induction of PGRP mRNA expression induced by these PAMPs in the cells. These findings suggested that bacterial PAMPs induced the expression of PGRPs, but not proinflammatory cytokines. Although the function of human PGRPs has not been clarified so far, in contrast to insect PGRPs, human PGRPs might be also involved in host defence against bacterial invasion without accompanying inflammatory responses. Further studies are required to elucidate the function of human PGRPs.
- Oral epithelial cells
- Peptidoglycan recognition proteins
- Toll-like receptors