Synergism between TLRs and NOD1/2 in oral epithelial cells.
Oral epithelium is the first barrier against oral bacteria in periodontal tissue. Oral epithelial cells constitutively express Toll-like receptors (TLRs) and NOD1/2, functional receptors which induce the production of antibacterial factors such as peptidoglycan recognition proteins (PGRPs) and beta-defensin 2, but not pro-inflammatory cytokines such as interleukin (IL)-8. In this study, we hypothesized that innate immune responses in the oral epithelium are enhanced in inflamed tissue. We found that NOD1 and NOD2 agonists, in combination with TLR agonists, synergistically induced production of PGRPs and of beta-defensin 2 in human oral epithelial cells via NF-kappaB. In contrast, co-stimulation with NOD1/2 and TLR ligands had no effect on the production of pro-inflammatory cytokines (IL-6, IL-8, and monocyte chemoattractant protein-1). These findings indicate that, in innate immune responses to invading microbes, a combination of signaling through TLRs and NODs leads to the synergistic activation of antibacterial responses in the oral epithelium.
Uehara
A
A
Department of Microbiology and Immunology, Tohoku University Graduate School of Dentistry, Sendai, Japan. kyoro@mail.tains.tohoku.ac.jp
Takada
H
H
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D004357:Drug Synergism; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D009055:Mouth / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D053474:Nod1 Signaling Adaptor Protein / Q000819:agonists / Q000276:immunology / Q000378:metabolism*; D053473:Nod2 Signaling Adaptor Protein / Q000819:agonists / Q000276:immunology / Q000378:metabolism*; D034622:RNA Interference / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology / Q000502:physiology; D051193:Toll-Like Receptors / Q000819:agonists / Q000276:immunology / Q000378:metabolism*; D023083:beta-Defensins / Q000276:immunology / Q000378:metabolism
D000276:Adjuvants, Immunologic; D002352:Carrier Proteins; C106641:DEFB4A protein, human; C119067:NOD1 protein, human; C429018:NOD2 protein, human; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein; D051193:Toll-Like Receptors; D023083:beta-Defensins; C118897:peptidoglycan recognition protein