Abstract
Sustained and non-resolved inflammation is a characteristic of periodontitis. Upon acute inflammation, gingival fibroblasts release cytokines to recruit immune cells to counter environmental stimuli. The intricate regulation of pro-inflammatory signaling pathways, such as NF-κB, is necessary to maintain periodontal homeostasis. Nonetheless, how inflammation is resolved has not yet been elucidated. In this study, 22 subtypes of taste receptor family 2 (TAS2Rs), as well as the downstream machineries of Gα-gustducin and phospholipase C-β2 (PLCβ2), were identified in human gingival fibroblasts (HGFs). Various bitter agonists could induce an intensive cytosolic Ca2+ response in HGFs. More importantly, TAS2R16 was expressed at a relatively high level, and its agonist, salicin, showed robust Ca2+ evocative effects in HGFs. Activation of TAS2R16 signaling by salicin inhibited the release of lipopolysaccharide (LPS)-induced pro-inflammatory cytokines, at least in part, by repressing LPS-induced intracellular cAMP elevation and NF-κB p65 nuclear translocation in HGFs. These findings indicate that TAS2Rs activation in HGFs may mediate endogenous pro-inflammation resolution by antagonizing NF-κB signaling, providing a novel paradigm and treatment target for the better management of periodontitis.
Highlights
Periodontitis is a chronic inflammatory disease that is triggered by the accumulation of dental plaques
As fibroblasts are predominant in gingival connective tissue and are closely involved in the inflammatory responses to environmental stimuli [5, 31, 32], we investigated the expression of TAS2Rs in human gingival fibroblasts (HGFs)
We investigated whether TAS2R16 activation impacted cytokine expression in HGFs in the context of LPS-induced inflammation
Summary
Periodontitis is a chronic inflammatory disease that is triggered by the accumulation of dental plaques. Periodontitis is the primary cause of tooth loss in adults. It affects oral health and has a close relationship with systemic diseases, such as diabetes mellitus, cardiovascular diseases, rheumatoid arthritis, etc [2]. Gingival fibroblasts are the predominant cells in gingival connective tissues, contributing to sustained inflammation in periodontal diseases [3, 4]. Sustained release of cytokines and immune cell recruitment will cause non-resolved inflammation, contributing to inflammatory tissue breakdown and the development of periodontitis. The regulation of cytokine release by fibroblasts during inflammation is mainly mediated by NF-kB signaling [7], while the mechanisms of periodontal inflammation resolution remain poorly understood
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call