Interleukin (IL)-17A synergistically enhances CC chemokine ligand 20 production in IL-1β-stimulated human gingival fibroblasts.
CC chemokine ligand 20 (CCL20) plays a pivotal role in the recruitment of T-helper (Th)-17 cells and thus in the development of periodontal disease, but the effect of simultaneous interleukin (IL)-17A and IL-1β stimulation on CCL20 production in human gingival fibroblasts (HGFs) are not known. In this study, we investigated the mechanisms of IL-1β- and IL-17A-induced CCL20 production in HGFs. IL-17A synergistically enhanced CCL20 production from IL-1β-stimulated HGFs in a concentration-dependent manner. Extracellular signal-regulated kinase (ERK) and inhibitor of nuclear factor (NF)-κB-α phosphorylation were increased in IL-1β- and IL-17A-stimulated HGFs. Inhibitors of or ERK and NF-κB decreased IL-1β- and IL-17A-induced CCL20 production. IL-1β stimulation elevated IL-17 receptor C expression on HGFs. These data suggest that IL-1β is actively related to Th17 cell migration into peripheral tissues to induce production of the Th17 chemokine, CCL20. Therefore, IL-1β might be a therapeutic target for Th17-related diseases, such as periodontal disease and arthritis.
Department of Conservative Dentistry, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan. hosokawa@dent.tokushima-u.ac.jp
Yoshitaka
Y
Hosokawa
Ikuko
I
Hosokawa
Kazumi
K
Ozaki
Hideaki
H
Nakae
Takashi
T
Matsuo
D015153:Blotting, Western; D002478:Cells, Cultured; D054418:Chemokine CCL20 / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D005881:Gingiva / Q000166:cytology; D006801:Humans; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D020381:Interleukin-17 / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D053722:Receptors, Interleukin-17 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013876:Thiophenes / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
C108355:CCL20 protein, human; D054418:Chemokine CCL20; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D020381:Interleukin-17; D053583:Interleukin-1beta; D016328:NF-kappa B; D011725:Pyridines; D053722:Receptors, Interleukin-17; C477523:SC 514; D013876:Thiophenes; D051550:I-kappa B Kinase; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one