SPRC Suppresses Experimental Periodontitis by Modulating Th17/Treg Imbalance.

Qian Peng,Shengcai Qi,Rong Zhou,Dongmei Lan,Yizhun Zhu,Shaohua Cong,Bingkun Zhao,Chao Yao,Jie Lin,Haixia Liu,Raorao Wang,Shen Tao

doi:10.3389/fbioe.2021.737334

Abstract

Object: The aims of the study were to explore the protective effects of S-propargyl-cysteine (SPRC) on periodontitis and to determine the underlying mechanisms. Methods: A rat periodontitis model was constructed by injecting LPS and SPRC (0, 25, and 50 mg/kg/d) was administered intraperitoneally. H2S and CSE level were detected. The alveolar bone level was evaluated by micro-CT, HE staining and methylene blue staining analysis. Inflammation-related factors, Treg and Th17 cells were detected by immunohistochemistry, RT-PCR, immunofluorescence, Western blot and flow cytometry. Phosphorylation levels of ERK1/2 and CREB were analysed. Results: The administration of SPRC significantly increased the expression of CSE in the gingival tissue and the concentration of endogenous H2S in the peripheral blood. Simultaneously, SPRC significantly inhibited the resorption of alveolar bone based on the H&E staining, micro-CT and methylene blue staining analysis. Compared with the periodontitis group, the levels of IL-17A, IL-10 were downregulated and IL-6,TGF-β1 were upregulated in the SPRC groups. In the SPRC group, the percentage of TH17 cells and the expression of ROR-γt were downregulated, while the percentage of Tregs and the expression of Foxp3 were upregulated accompanied with inhibition of phosphorylation ERK1/2 and CREB. Conclusion: SPRC can prevent the progression of periodontitis by regulating the Th17/Treg balance by inhibition of the ERK/CREB signalling pathway.

Highlights

Periodontitis (PD) is a prevalent chronic inflammatory diseases and caused by infection of bacteria on the surface of teeth,which is characterized by destruction of soft and hard periodontal tissue (Graves et al, 2006)
These results suggest that imbalance in Th17/Treg cells has an important function in the pathogenesis of periodontitis (Rose et al, 2015)
Compared with the control group, periodontal bone resorption was significantly increased in the LPS group by methylene stereomicroscopy and haematoxylin and eosin (H&E) (Figures 1B–E, *p < 0.05), which showed that the rat periodontitis model was successfully constructed

Summary

Introduction

Periodontitis (PD) is a prevalent chronic inflammatory diseases and caused by infection of bacteria on the surface of teeth,which is characterized by destruction of soft and hard periodontal tissue (Graves et al, 2006). Retinoic acid-related orphan receptor gamma transcription (RORγt) factor, a predominantly proinflammatory mediator, is expressed on Th17 cells and act a crucial role in immune-mediated diseases and tissue injury by producing the characteristic cytokine IL-17 (Lee, 2018). Regulatory T cell (Treg) expression of Forkhead box p3 (Foxp3), which has a regulatory function and suppresses effector T cell function, exerts an antiinflammatory role by secreting anti-inflammatory cytokines (such as transforming growth factor-β (TGF-β) and IL-10) to help balance of immune homeostasis which can alleviate immune-mediated tissue injury (Sakaguchi, 2003; Lee, 2018; Deng et al, 2019). The activiation of Th17 cells can be inhibited by the migration of Tregs These results suggest that imbalance in Th17/Treg cells has an important function in the pathogenesis of periodontitis (Rose et al, 2015). Regulating the TH17/Treg balance is a useful target for developing new methods for treating periodontitis

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Conclusion