PRDX6 alleviates lipopolysaccharide-induced inflammation and ferroptosis in periodontitis

Authors

  • Wen-Ying Yang a College & Hospital of Stomatology, Anhui Medical University, Key Laboratory of Oral Diseases Research of Anhui Province, Hefei, China
  • Xiang Meng a College & Hospital of Stomatology, Anhui Medical University, Key Laboratory of Oral Diseases Research of Anhui Province, Hefei, China
  • Yue-Rong Wang a College & Hospital of Stomatology, Anhui Medical University, Key Laboratory of Oral Diseases Research of Anhui Province, Hefei, China
  • Qing-Qing Wang a College & Hospital of Stomatology, Anhui Medical University, Key Laboratory of Oral Diseases Research of Anhui Province, Hefei, China;b Periodontal Department, Anhui Stomatology Hospital affiliated to Anhui Medical University, Hefei, China
  • Xin He a College & Hospital of Stomatology, Anhui Medical University, Key Laboratory of Oral Diseases Research of Anhui Province, Hefei, China; b Periodontal Department, Anhui Stomatology Hospital affiliated to Anhui Medical University, Hefei, China
  • Xiao-Yu Sun a College & Hospital of Stomatology, Anhui Medical University, Key Laboratory of Oral Diseases Research of Anhui Province, Hefei, China; b Periodontal Department, Anhui Stomatology Hospital affiliated to Anhui Medical University, Hefei, China
  • Nan Cheng a College & Hospital of Stomatology, Anhui Medical University, Key Laboratory of Oral Diseases Research of Anhui Province, Hefei, China; b Periodontal Department, Anhui Stomatology Hospital affiliated to Anhui Medical University, Hefei, China
  • Lei Zhang a College & Hospital of Stomatology, Anhui Medical University, Key Laboratory of Oral Diseases Research of Anhui Province, Hefei, China; b Periodontal Department, Anhui Stomatology Hospital affiliated to Anhui Medical University, Hefei, China

DOI:

https://doi.org/10.1080/00016357.2022.2047780

Keywords:

PRDX6, ferroptosis, periodontitis, LPS

Abstract

Objective

Periodontitis is a progressive and inflammatory oral disease and results in the damage of the supporting tissues of teeth. Peroxiredoxin 6 (PRDX6) is an antioxidant enzyme identified as a regulator in ferroptosis. This study aimed to investigate whether PRDX6 could protect human gingival fibroblasts (HGFs) from lipopolysaccharide (LPS)-induced inflammation and its mechanisms.

Material and methods

Both inflamed and non-inflamed human gingival tissues were collected to assess the expression of PRDX6 and nuclear factor erythropoietin 2-related factor 2 (NRF2) by Immunohistochemistry and Western blotting. Furthermore, the molecular mechanisms of PRDX6 have been clarified in PRDX6 silenced cells. The inflammatory cytokines in HGFs were measured by RT-qPCR and ELISA. The lipid hydroperoxide (LOOH) was detected by C11-BODIPY.

Results

The expression of PRDX6 and NRF2 were decreased in gingival tissues of severe periodontitis patients. The increased LPS-induced LOOH and inflammatory cytokines were found in PRDX6 knockdown HGFs. Besides, the inhibition of ferroptosis or PRDX6 phospholipase A2 activity (PLA2) alleviated LPS-induced inflammatory cytokines and LOOH. However, inhibiting NRF2 signalling upregulated those in HGFs.

Conclusions

Therefore, this study provided a new mechanistic insight that PRDX6, regulated by the NRF2 signalling, alleviates LPS-induced inflammation and ferroptosis in human gingival fibroblasts.

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Published

2022-10-03

Issue

Vol. 80 No. 7 (2022): Acta Odontologica Scandinavica

Section

Articles