Roles of TLR2, TLR4, NOD2, and NOD1 in pulp fibroblasts.
Pulp fibroblasts express various pro-inflammatory mediators leading to marked infiltration of inflammatory cells in the progression of pulpitis. We hypothesized that pulp fibroblasts play roles in the recognition of invaded caries-related bacteria and the subsequent innate immune responses. We found clear expressions of TLR2, NOD1, and NOD2 and a faint expression of TLR4 in human dental pulp fibroblasts (HDPF) by RT-PCR and flow cytometry. We also observed that various pro-inflammatory mediators, including cytokines, chemokines, adhesion molecules, prostaglandin E(2) and its key enzyme COX-2, not iNOS or caspase-1, were markedly up-regulated by stimulation with these TLR and NOD agonists. More over, the NOD2 agonist acted synergistically with the TLR2, not the TLR4, agonist to stimulate the production of pro-inflammatory mediators in HDPF. These findings indicate that TLR2, TLR4, NOD2, and NOD1 in HDPF are functional receptors, and NOD2 is a modulator of signals transmitted through TLR2 in pulpal immune responses, leading to progressive pulpitis.
Hirao
K
K
Department of Conservative Dentistry, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8504, Japan.
Yumoto
H
H
Takahashi
K
K
Mukai
K
K
Nakanishi
T
T
Matsuo
T
T
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology; D017209:Apoptosis / Q000276:immunology*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000032:analysis; D054357:Chemokine CXCL10 / Q000032:analysis; D051546:Cyclooxygenase 2 / Q000276:immunology; D003782:Dental Pulp / Q000166:cytology / Q000276:immunology*; D003960:Diaminopimelic Acid / Q000031:analogs & derivatives; D015232:Dinoprostone / Q000032:analysis; D004926:Escherichia coli; D005347:Fibroblasts / Q000276:immunology*; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology; D015850:Interleukin-6 / Q000032:analysis; D016209:Interleukin-8 / Q000032:analysis; D055666:Lipopeptides / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D053474:Nod1 Signaling Adaptor Protein / Q000032:analysis* / Q000037:antagonists & inhibitors; D053473:Nod2 Signaling Adaptor Protein / Q000032:analysis* / Q000037:antagonists & inhibitors; D011671:Pulpitis / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D013295:Streptococcus mutans / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000032:analysis* / Q000037:antagonists & inhibitors; D051197:Toll-Like Receptor 4 / Q000032:analysis* / Q000037:antagonists & inhibitors; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis
C111835:CCL2 protein, human; C114753:CXCL10 protein, human; D018932:Chemokine CCL2; D054357:Chemokine CXCL10; D018836:Inflammation Mediators; D015850:Interleukin-6; D016209:Interleukin-8; D055666:Lipopeptides; D008070:Lipopolysaccharides; C119067:NOD1 protein, human; C429018:NOD2 protein, human; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein; C508075:Pam(3)CSK(4) peptide; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D019010:Vascular Cell Adhesion Molecule-1; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D003960:Diaminopimelic Acid; C034331:N(2)-(gamma-D-glutamyl)-meso-2,2'-diaminopimelic acid; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D015232:Dinoprostone