Ropinirole inhibits inflammatory cytokine production in gingival epithelial cells and suppresses alveolar bone loss in an experimental rat model of periodontitis

Abstract

The present study explored whether the dopamine 2-like receptor agonist, ropinirole, a drug used for treating Parkinson's disease, suppresses neutrophilic inflammation and alveolar bone loss in an experimental rat model of periodontitis. Periodontitis is a neutrophilic inflammatory disease caused by periodontal pathogens. An excessive T helper (Th)17 immune response is involved in the progression of periodontitis, and interleukin (IL)-17 promotes the exacerbation of inflammation and alveolar bone destruction. Recent evidence has suggested that dopamine signaling plays a key role in Th17 cell differentiation, and that dopamine 2-like receptor agonists suppress cytokine production from Th17 cells. We previously demonstrated that tannic acid, which is a dopamine 2-like receptor agonist, inhibits alveolar bone resorption in an experimental model of periodontitis. The present study used a carrageenan-induced rat model of periodontitis with or without ropinirole. Micro-computed tomography analysis was performed. Cells of the murine gingival epithelial cell line GE1 were stimulated with carrageenan and IL-17A in the presence or absence of ropinirole. The anti-inflammatory effect of ropinirole was analyzed using reverse transcription-quantitative PCR and enzyme-linked immunosorbent assay. Subsequently, in the carrageenan-induced rat model of periodontitis, alveolar bone resorption was observed in the maxillary second molar by micro-computed tomography analysis. Intriguingly, ropinirole suppressed the alveolar bone destruction. The expression levels of C-X-C motif chemokine ligand 1 (CXCL1) and IL-17 receptor A (IL-17RA) in GE1 cells were increased by carrageenan, and CXCL1 expression in GE1 cells was upregulated under IL-17A stimulation. Moreover, ropinirole inhibited CXCL1 and IL-17RA expression in GE1 cells in the presence of IL-17A and carrageenan. Finally, haloperidol promoted CXCL1 expression in GE1 cells in the presence of carrageenan. Overall, these findings suggested that ropinirole suppressed neutrophilic inflammation and alveolar bone destruction in periodontitis by inhibiting CXCL1 expression in gingival epithelial cells through the dopamine 2-like receptor. Thus, ropinirole shows promise as a drug for the treatment of periodontitis.

Ropinirole suppresses LPS-induced periodontal inflammation by inhibiting the NAT10 in an ac4C-dependent manner

“…There is rapidly growing evidence for the influence of inflammation on the development and progression of Parkinson's disease, and Ropinirole has been reported to regulate inflammatory factors in serum of patients with Parkinson's disease [16]. In this study, Ropinirole protected HGFs from LPS induced injury by suppressing inflammatory response, which is in line with the study of Isozaki et al [10]. Moreover, Ropinirole can bind to NAT10 according to the the molecular docking results.…”

“…Ropinirole hydrochloride, a dopamine D2 receptor agonist, is commonly used for Parkinson's disease [8,9]. Previous studies have shown that Ropinirole inhibits the expression of CXCL1 in gingival epithelial cells through dopamine-like receptors, thereby inhibiting neutrophil inflammation and alveolar bone destruction in a murine periodontitis model [10]. Inhibiting inflammation can promote alveolar bone regeneration and repair to treat periodontitis [11].…”

Dopamine Receptor 1 Treatment Promotes Epithelial Repair of Corneal Injury by Inhibiting NOD-Like Receptor Protein 3–Associated Inflammation

“… 8 Despite the acknowledged anti-inflammatory role of DRD1 in both in vitro and in vivo settings involving microglial cells, its potential therapeutic implications for the repair of corneal epithelial cells in inflamed and injured corneal tissues remain largely unexplored. Recent studies have reported that ropinirole can inhibit the expression of C-X-C motif chemokine ligand 1 (CXCL1) in gingival epithelial cells via dopamine receptors, leading to the suppression of neutrophil inflammation, 9 but the specific signaling pathway associated with DRD1 in the regulation of NLRP3-driven inflammation in epithelial cells remains unexplored.…”