title: Synergy of TLR2 and H1R on Cox-2 Activation in Pulpal Cells.
abstract: Although pulp fibroblasts are a major cell type in dental pulp, their roles in microbial recognition and pulpal inflammation are not well-understood. Considering the pivotal role of Toll-like receptors (TLRs) in the recognition of micro-organisms, we hypothesized that TLRs on pulp fibroblasts may induce inflammatory signals in dental pulp. In human pulp fibroblasts, TLR2, 3, 4, and 5 were constitutively expressed. Stimulation of TLR2 and 3 induced the expression of pro-inflammatory genes such as CXCL10, CCL5, and/or Cox-2 in pulp fibroblasts. Interestingly, histamine synergistically activated TLR2-mediated Cox-2 expression and PGE(2) production. The synergistic effect of histamine is mediated by histamine receptor-1 (H1R). Studies on the intra-cellular signaling pathways revealed that p38 activation is required for the synergistic activation of Cox-2 by TLR2 and histamine. Analysis of these data suggests that TLR2 on pulp fibroblasts, in concert with H1R, can induce an inflammatory response during microbial infection in dental pulp.
authors.affiliation: Dental Research Institute, Department of Oral Physiology, Seoul National University School of Dentistry, Yeongun-dong, Jongno-gu, Republic of Korea.
authors.forename: C
authors.initials: C
authors.lastname: Park
authors.forename: S Y
authors.initials: SY
authors.lastname: Lee
authors.forename: H J
authors.initials: HJ
authors.lastname: Kim
authors.forename: K
authors.initials: K
authors.lastname: Park
authors.forename: J S
authors.initials: JS
authors.lastname: Kim
authors.forename: S J
authors.initials: SJ
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D015153:Blotting, Western; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000096:biosynthesis; D054357:Chemokine CXCL10 / Q000096:biosynthesis; D002744:Chlorpheniramine / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D003782:Dental Pulp / Q000166:cytology / Q000201:enzymology* / Q000276:immunology; D015232:Dinoprostone / Q000096:biosynthesis; D004789:Enzyme Activation; D005347:Fibroblasts / Q000201:enzymology / Q000276:immunology; D006632:Histamine / Q000502:physiology; D017442:Histamine Agonists / Q000494:pharmacology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D011969:Receptors, Histamine H1 / Q000276:immunology / Q000502:physiology*; D013682:Teichoic Acids / Q000494:pharmacology; D051195:Toll-Like Receptor 2 / Q000819:agonists / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D051198:Toll-Like Receptor 5 / Q000096:biosynthesis; D055815:Young Adult; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology
chemical_list: D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D017442:Histamine Agonists; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011969:Receptors, Histamine H1; D013682:Teichoic Acids; D051195:Toll-Like Receptor 2; D051198:Toll-Like Receptor 5; D002744:Chlorpheniramine; C009900:lipoteichoic acid; D006632:Histamine; D051546:Cyclooxygenase 2; D048051:p38 Mitogen-Activated Protein Kinases; D015232:Dinoprostone