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.