PRDX6 alleviates lipopolysaccharide-induced inflammation and ferroptosis in periodontitis

  • Acta Odontol Scand. 2022 Oct;80(7):535-546. doi: 10.1080/00016357.2022.2047780.
Wen-Ying Yang  1 ,  Xiang Meng  1 ,  Yue-Rong Wang  1 ,  Qing-Qing Wang  1  2 ,  Xin He  1  2 ,  Xiao-Yu Sun  1  2 ,  Nan Cheng  1  2 ,  Lei Zhang  1  2
Affiliations
  • 1. College & Hospital of Stomatology, Anhui Medical University, Key Laboratory of Oral Diseases Research of Anhui Province, Hefei, China.
  • 2. Periodontal Department, Anhui Stomatology Hospital affiliated to Anhui Medical University, Hefei, China.
PMID: 35723029 DOI: 10.1080/00016357.2022.2047780
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.

Keywords
LPS; PRDX6; ferroptosis; periodontitis.
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