A20 alleviated caspase-1-mediated pyroptosis and inflammation stimulated by Porphyromonas gingivalis lipopolysaccharide and nicotine through autophagy enhancement
Periodontitis is the leading cause of tooth loss, and patients with smoking habits are at an increased risk of developing periodontitis. A20 (the tumor necrosis factor alpha-induced protein 3, TNFAIP3) is one of the key regulators of inflammation and cell death in numerous tissues. Emerging research...
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Published in | Human cell : official journal of Human Cell Research Society Vol. 35; no. 3; pp. 803 - 816 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Singapore
Springer Nature Singapore
01.05.2022
Springer Nature B.V |
Subjects | |
Online Access | Get full text |
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Summary: | Periodontitis is the leading cause of tooth loss, and patients with smoking habits are at an increased risk of developing periodontitis. A20 (the tumor necrosis factor alpha-induced protein 3, TNFAIP3) is one of the key regulators of inflammation and cell death in numerous tissues. Emerging researches indicated A20 as a fundamental molecule in the periodontal tissue. This study was to evaluate the role of A20 against cell death and inflammation in periodontitis and to elucidate the underlying mechanisms. In our study, western blot, autophagy detection, and transmission electron microscopy showed that lipopolysaccharide from
Porphyromonas gingivalis
(
Pg
.LPS) and nicotine (NI) could enhance the activation of autophagy.
Pg
.LPS and NI induce the pyroptosis of human periodontal ligament cells (hPDLCs), as evidenced by the decrease of membrane integrity and the increase of NLRP3, GSDMD, GSDMD-N, caspase-1 activity, and the pro-inflammatory cytokines of IL-1β, IL-6, TNF-α. Further researches were focused on that A20, an ubiquitin-editing enzyme, was linked to hPDLCs pyroptosis. Overexpression or silencing A20 could diminish or aggravate pyroptosis in hPDLCs by the modulation of autophagy. The above results demonstrated that A20 dictated the cross-talk between pyroptosis and autophagy. Overexpression of A20 enhanced autophagy to reduce pyroptosis, and thus alleviating inflammation, suggesting that A20 may be a potent target in the treatment of periodontitis. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1749-0774 0914-7470 1749-0774 |
DOI: | 10.1007/s13577-022-00678-5 |