title: Tumor necrosis factor-like weak inducer of apoptosis increases CC chemokine ligand 20 production in interleukin 1β-stimulated human gingival fibroblasts.
abstract: CC chemokine ligand 20 (CCL20) is related to T-helper (Th)-17 cell migration, and Th17 cells play important roles in exacerbation in periodontal disease. However, the effect of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) on CCL20 production is unknown. In this study, we examined the mechanisms of TWEAK in combination with interleukin (IL)-1β-induced CCL20 production in human gingival fibroblasts (HGFs). TWEAK alone did not induce CCL20 production in HGFs. However, TWEAK enhanced CCL20 expression from IL-1β-stimulated HGFs in a dose-dependent manner. Inhibitors of p38 mitogen-activated protein kinase, extracellular signal-regulated kinase (ERK), protein kinase B (Akt), and nuclear factor κB (NF-κB) significantly inhibited CCL20 production in TWEAK and IL-1β-stimulated HGFs. Western blot analysis revealed that phosphorylations of ERK, Akt, and inhibitor of NF-κB were enhanced in TWEAK and IL-1β-treated HGFs. These data suggest that TWEAK is positively related to Th17 cell migration in periodontally diseased tissues to enhance CCL20 production in IL-1β-stimulated HGFs.
authors.affiliation: Department of Conservative Dentistry, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima 770-8504, 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: Satoru
authors.initials: S
authors.lastname: Shindo
authors.forename: Kazumi
authors.initials: K
authors.lastname: Ozaki
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nakae
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsuo
mesh_terms: D002465:Cell Movement; D054418:Chemokine CCL20 / Q000096:biosynthesis* / Q000276:immunology; D000074049:Cytokine TWEAK; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000276:immunology; D005347:Fibroblasts / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D005881:Gingiva / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000276:immunology / Q000494:pharmacology*; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D010510:Periodontal Diseases / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D061251:Primary Cell Culture; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology; D048069:Tumor Necrosis Factors / Q000276:immunology / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000276:immunology
chemical_list: C108355:CCL20 protein, human; D054418:Chemokine CCL20; D000074049:Cytokine TWEAK; D053583:Interleukin-1beta; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; C109743:TNFSF12 protein, human; D048069:Tumor Necrosis Factors; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases