title: Beyond toll-like receptors: Porphyromonas gingivalis induces IL-6, IL-8, and VCAM-1 expression through NOD-mediated NF-κB and ERK signaling pathways in periodontal fibroblasts.
abstract: To investigate whether oligomerization domains (NODs) are involved in Porphyromonas gingivalis-induced interleukin (IL)-6, IL-8, and vascular cell adhesion molecule (VCAM)-1 expression beyond Toll-like receptors (TLRs), we investigated the role of NOD1/2 in P. gingivalis-induced IL-6, IL-8, and VCAM-1 expression in human gingival fibroblasts (hGFs) and periodontal ligament cells (hPDLCs). The mechanism was explored by activation and silence of NODs, electrophoretic mobility shift assay (EMSA), and pathway blockade assays. Results showed that P. gingivalis could induce NOD1, NOD2, IL-6, IL-8, and VCAM-1 expression in hGFs and hPDLs at mRNA and protein levels. Activation of NOD1/2 by agonists could clearly upregulate the expression of these genes, while silence of NOD1/2 could remarkably attenuate them. EMSA and blockade of NF-κB and extracellular-signal-regulated kinase (ERK)1/2 pathway assays also verified that the two pathways were involved in NOD1/2-mediated IL-6, IL-8, and VCAM-1 expression. In conclusion, our findings demonstrated that P. gingivalis induced IL-6, IL-8, and VCAM-1 expression in hGFs and hPDLCs through NOD1/2-mediated NF-κB and ERK1/2 signaling pathways beyond TLRs.
authors.affiliation: Department of Periodontology, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing, 100081, China.
authors.forename: Jianru
authors.initials: J
authors.lastname: Liu
authors.forename: Yixiang
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiangying
authors.initials: X
authors.lastname: Ouyang
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology; D000328:Adult; D002478:Cells, Cultured; D003960:Diaminopimelic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology / Q000276:immunology / Q000382:microbiology*; D005881:Gingiva / Q000187:drug effects / Q000201:enzymology / Q000276:immunology / Q000382:microbiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D053472:Nod Signaling Adaptor Proteins / Q000235:genetics / Q000378:metabolism*; D053474:Nod1 Signaling Adaptor Protein / Q000378:metabolism; D053473:Nod2 Signaling Adaptor Protein / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D016966:Porphyromonas gingivalis / Q000276:immunology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D014162:Transfection; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: C508606:CXCL8 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; C555437:L-Ala-gamma-D-Glu-meso-diaminopimelic acid; D016328:NF-kappa B; C119067:NOD1 protein, human; C429018:NOD2 protein, human; D053472:Nod Signaling Adaptor Proteins; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein; D009842:Oligopeptides; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D019010:Vascular Cell Adhesion Molecule-1; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D003960:Diaminopimelic Acid; D048049:Extracellular Signal-Regulated MAP Kinases