title: Tea catechins reduce inflammatory reactions via mitogen-activated protein kinase pathways in toll-like receptor 2 ligand-stimulated dental pulp cells.
abstract: OBJECTIVE
  In this study, we evaluated whether catechins could inhibit the expression of pro-inflammatory mediators induced by dental caries-related bacteria, Streptococci, or pathogen-associated molecular patterns (PAMPs) stimulation in human dental pulp fibroblasts (HDPF). We further determined the mechanisms of the anti-inflammatory activity of catechins.
  
  
  METHODS
  Streptococci or PAMP-stimulated HDPF were treated with catechin, and then the expression and production of pro-inflammatory mediators were determined by RT-PCR and ELISA. Furthermore, the signal transduction pathways activated with toll-like receptor (TLR)2 ligand were assessed by Immunoblot and ELISA using blocking assay with specific inhibitors.
  
  
  RESULTS
  Increased expressions of pro-inflammatory mediators are found in inflamed dental pulp, especially in HDPF. We recently reported that dental pulpal innate immune responses may mainly result from the predominantly-expressed TLR2 signaling. Catechins, polyphenolic compounds in green tea, exert protective and healing effects through multiple mechanisms, including antioxidative and anti-inflammatory effects. However, there are no reports concerning the effects of catechins on dental pulp. In this study, we demonstrated that the up-regulated expressions of IL-8 or PGE(2) in Streptococci or PAMP-stimulated HDPF were inhibited by catechins, (-)-epicatechin gallate (ECG) and (-)-epigallocatechin gallate (EGCG). In TLR2 ligand-stimulated HDPF, specific inhibitors of extracellular signal regulated kinase (ERK)1/2, p38, c-jun NH(2)-terminal kinase (SAP/JNK), NF-kappaB or catechins markedly reduced the level of pro-inflammatory mediators and the phosphorylation of these signal transduction molecules was suppressed by catechins.
  
  
  CONCLUSIONS
  These findings suggest that catechins might be useful therapeutically as an anti-inflammatory modulator of dental pulpal inflammation.
authors.affiliation: Department of Conservative Dentistry, Institute of Health Biosciences, The University of Tokushima Graduate School, Japan.
authors.forename: Kouji
authors.initials: K
authors.lastname: Hirao
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Yumoto
authors.forename: Tadashi
authors.initials: T
authors.lastname: Nakanishi
authors.forename: Kayo
authors.initials: K
authors.lastname: Mukai
authors.forename: Kanako
authors.initials: K
authors.lastname: Takahashi
authors.forename: Daisuke
authors.initials: D
authors.lastname: Takegawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsuo
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002478:Cells, Cultured; D003782:Dental Pulp / Q000166:cytology / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology; D018836:Inflammation Mediators / Q000378:metabolism; D008024:Ligands; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051192:Receptors, Pattern Recognition / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D013291:Streptococcus / Q000276:immunology; D013662:Tea / Q000737:chemistry*; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D018836:Inflammation Mediators; D008024:Ligands; D051192:Receptors, Pattern Recognition; D013662:Tea; D051195:Toll-Like Receptor 2; D002392:Catechin; C062669:epicatechin gallate; C045651:epigallocatechin gallate; D020928:Mitogen-Activated Protein Kinases