title: Tea polyphenols inhibit IL-6 production in tumor necrosis factor superfamily 14-stimulated human gingival fibroblasts.
abstract: IL-6 is well recognized to be a potent bone resorptive agent and thus in the development of periodontal disease. Epigallocatechin gallate (EGCG) and epicatechin gallate (ECG), the major catechins in green tea, and theaflavin-3,3'-digallate (TFDG), polyphenol in black tea, have multiple beneficial effects, but the effects of catechins and theaflavins on IL-6 production in human gingival fibroblasts (HGFs) are not known. In this study, we investigated the mechanisms by which EGCG, ECG, and TFDG inhibit tumor necrosis factor superfamily 14 (TNFSF14)-induced IL-6 production in HGFs. We detected TNFSF14 mRNA expression in human diseased periodontal tissues. TNFSF14 increased IL-6 production in HGFs in a concentration-dependent manner. EGCG, ECG, and TFDG prevented TNFSF14-mediated IL-6 production in HGFs. EGCG, ECG, and TFDG prevented TNFSF14-induced extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and nuclear factor-kappaB activation in HGFs. Inhibitors of ERK, JNK, and nuclear factor-kappaB decreased TNFSF14-induced IL-6 production. In addition, EGCG, ECG, and TFDG attenuated TNFSF14 receptor expression on HGFs. These data provide a novel mechanism through which the green tea and black tea polyphenols could be used to provide direct benefits in periodontal disease.
authors.affiliation: Department of Conservative Dentistry, The University of Tokushima Graduate School, Tokushima, Japan. hosokawa@dent.tokushima-u.ac.jp
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Hosokawa
authors.forename: Ikuko
authors.initials: I
authors.lastname: Hosokawa
authors.forename: Kazumi
authors.initials: K
authors.lastname: Ozaki
authors.forename: Tadashi
authors.initials: T
authors.lastname: Nakanishi
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nakae
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsuo
mesh_terms: D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D044946:Biflavonoids / Q000494:pharmacology; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002478:Cells, Cultured; D055113:Chronic Periodontitis / Q000188:drug therapy / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D005881:Gingiva / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010636:Phenols / Q000494:pharmacology*; D059808:Polyphenols; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013662:Tea / Q000737:chemistry*; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14 / Q000235:genetics / Q000502:physiology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D044946:Biflavonoids; D004791:Enzyme Inhibitors; D005419:Flavonoids; C508600:IL6 protein, human; D015850:Interleukin-6; D010636:Phenols; D059808:Polyphenols; D012333:RNA, Messenger; C505914:TNFSF14 protein, human; D013662:Tea; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; C077197:theaflavin digallate; D005707:Gallic Acid; D002392:Catechin; C062669:epicatechin gallate; C045651:epigallocatechin gallate