Chemically synthesized pathogen-associated molecular patterns increase the expression of peptidoglycan recognition proteins via toll-like receptors, NOD1 and NOD2 in human oral epithelial cells.
Peptidoglycan recognition proteins (PGRPs), a novel family of pattern recognition molecules (PRMs) in innate immunity conserved from insects to mammals, recognize bacterial cell wall peptidoglycan (PGN) and are suggested to act as anti-bacterial factors. In humans, four kinds of PGRPs (PGRP-L, -Ialpha, -Ibeta and -S) have been cloned and all four human PGRPs bind PGN. In this study, we examined the possible regulation of the expression of PGRPs in oral epithelial cells upon stimulation with chemically synthesized pathogen-associated molecular patterns (PAMPs) in bacterial cell surface components: Escherichia coli-type tryacyl lipopeptide (Pam3CSSNA), E. coli-type lipid A (LA-15-PP), diaminopimelic acid containing desmuramyl peptide (gamma-D-glutamyl-meso-DAP; iE-DAP), and muramyldipeptide (MDP). These synthetic PAMPs markedly upregulated the mRNA expression of the four PGRPs and cell surface expression of PGRP-Ialpha and -Ibeta, but did not induce either mRNA expression or secretion of inflammatory cytokines, in oral epithelial cells. Suppression of the expression of Toll-like receptor (TLR)2, TLR4, nucleotide-binding oligomerization domain (NOD)1 and NOD2 by RNA interference specifically inhibited the upregulation of PGRP mRNA expression induced by Pam3CSSNA, LA-15-PP, iE-DAP and MDP respectively. These PAMPs definitely activated nuclear factor (NF)-kappaB in the epithelial cells, and suppression of NF-kappaB 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, in oral epithelial cells, and the PGRPs might be involved in host defence against bacterial invasion without accompanying inflammatory responses.
Uehara
A
A
Department of Microbiology and Immunology, Tohoku University Graduate School of Denstistry, Sendai, Japan.
Sugawara
Y
Y
Kurata
S
S
Fujimoto
Y
Y
Fukase
K
K
Kusumoto
S
S
Satta
Y
Y
Sasano
T
T
Sugawara
S
S
Takada
H
H
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000737:chemistry / Q000494:pharmacology; D048868:Adaptor Proteins, Signal Transducing / Q000819:agonists / Q000378:metabolism*; D002352:Carrier Proteins / Q000096:biosynthesis*; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D004075:Diglycerides / Q000737:chemistry / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology; D004926:Escherichia coli / Q000737:chemistry* / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000819:agonists / Q000378:metabolism*; D008050:Lipid A / Q000737:chemistry / Q000494:pharmacology; D009061:Mouth Mucosa / Q000166:cytology / Q000378:metabolism* / Q000382:microbiology; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D010457:Peptidoglycan / Q000378:metabolism; D010867:Pimelic Acids / Q000737:chemistry / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering / Q000235:genetics; D051195:Toll-Like Receptor 2 / Q000819:agonists / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000819:agonists / Q000235:genetics; D015854:Up-Regulation
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D016207:Cytokines; D004075:Diglycerides; C460864:FSL-1 lipoprotein, synthetic; D047908:Intracellular Signaling Peptides and Proteins; D008050:Lipid A; C119067:NOD1 protein, human; C429018:NOD2 protein, human; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein; D009842:Oligopeptides; D010457:Peptidoglycan; D010867:Pimelic Acids; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; C118897:peptidoglycan recognition protein; D000119:Acetylmuramyl-Alanyl-Isoglutamine