NADPH Oxidase 4 Mediates IL-1β induced CCL20 in Human Gingival Fibroblasts

Periodontal diseases have a high prevalence in Taiwan. The primary cause of periodontitis is poor or ineffective oral hygiene, which leads to the accumulation of bacterial matrix, called dental plaque. Subgingival micro-organisms would deposit endotoxin and cause further inflammation in the gum tissues and progressive bone loss. During the inflammation process, a lot of cytokines will increases in expression. One of them is Interleukin-1β (IL-1β). IL-1βhas the ability to induce Chemokine (C-C motif) ligand 20 (CCL20), and CCL20 can attract T helper cell to the inflamed gingival tissue, causing IL-17 to increase. Il-17 can promote osteoclast activity and subsequently escalate bone resorption. The overall mechanism involved in the induction of CCL20 by IL-1β is still unknown and it is the aim of our study to further investigate this signaling pathway. Previous studies had shown that IL-1βinduce CCL20 in Human gingival fibroblast (HGF) via a NF-κB dependent pathway. We discovered the NOX4 inhibitor, Plumbagin and ROS inhibitor, NAC can inhibit the above mentioned pathway. And IL-1β can induce NOX4 and ROS in HGF as well. This proved that the signaling pathway of CCL20 induction by IL-1βis NOX4 dependent. Furthermore, we also discovered that Curcumin has the ability to inhibit IL-1β from inducing NOX4 and CCL20 in HGF. This finding may be useful in developing future adjunctive therapy in treating periodontal disease