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

Yuta Isozaki; Tsuyoshi Sato; Rie Takagi; Ko Ito; Michihiko Usui; Masaaki Kawano; Sho Matsushita

doi:10.3892/etm.2022.11777

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

Exp Ther Med. 2022 Dec 29;25(2):78. doi: 10.3892/etm.2022.11777. eCollection 2023 Feb.

Authors

Yuta Isozaki¹, Tsuyoshi Sato¹, Rie Takagi², Ko Ito¹, Michihiko Usui³, Masaaki Kawano², Sho Matsushita²

Affiliations

¹ Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Saitama Medical University, Iruma, Saitama 350-0495, Japan.
² Department of Allergy and Immunology, Faculty of Medicine, Saitama Medical University, Iruma, Saitama 350-0495, Japan.
³ Division of Periodontology, Department of Cardiology and Periodontology, Kyushu Dental University, Kitakyusyu, Fukuoka 803-8530, Japan.

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.

Keywords: CXCL1; IL-17; dopamine receptor; neutrophil inflammation; periodontitis; ropinirole.

Grants and funding

Funding: This work was supported by a Grant-in-Aid for Young Researchers from Saitama Medical University Hospital (grant no. 30-E-1-03) and JSPS KAKENHI (grant no. 22K17065).