Th17 cytokines enhance CCL20 production by human gingival fibroblasts

CC chemokine ligand 20 (CCL20) is a cytokine related to T helper 17 cells (Th17) migration. It has been reported that Th17 cells are related to bone resorption in some diseases, such as arthritis. Objectives: In this study, we examined the effects of Th17 cytokines, such as interleukin (IL)-17A, IL-17F and IL-22, on CCL20 production by human gingival fibroblasts (HGFs). Methods: We used HGFs isolated from three clinically healthy gingiva during routine distal wedge surgical procedures. The HGFs that grew from the gingiva were cultured primarily on 100 mm2 uncoated plastic dishes in Dulbecco's modified Eagle medium supplemented with 10% fetal bovine serum and antibiotics at 37°C in humidified air with 5% CO2. Confluent cells were transfered and cultured for use in the present study. HGFs were stimulated with IL-17A, IL-17F, IL-22, IL-1beta, TNF-alpha, IL-4, IL-13, IL-10, and interferon (IFN)-gamma for 24 h. The supernatants from HGFs were collected and CCL20 concentration of the culture supernatants was measured in triplicate with enzyme-linked immunosorbent assay (ELISA). Results: IL-17A slightly induced CCL20 production by HGFs. However, single stimuli of IL-17F and IL-22 did not induce CCL20. On the other hands, IL-17A, IL-17F and IL-22 synergistically enhanced IL-1beta or TNF-alpha-induced CCL20 production by HGFs. IL-4, IL-13 and IFN-gamma inhibited CCL20 production by IL-17A-treated HGFs. Conclusions: Our results suggest that various cytokines modify CCL20 production by HGFs in periodontal tissues, and CCL20 by HGFs might control Th17 cells migration into diseased periodontal tissues. This work was supported by a Grant-in-Aid for Scientific Research (B) (19791616) from the Japan Society for the Promotion of Science.