Synoviolin alleviates GSDMD‐mediated periodontitis by suppressing its stability

Abstract Introduction Inflammasome and pyroptosis play important roles in periodontitis. Gasdermin D (GSDMD), a key factor in pyroptosis, is cleaved by caspase‐1 and regulated by ubiquitination. Synoviolin is a ubiquitin E3 ligase that interacts with GSDMD. In this study, the effects of Synoviolin o...

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Main Authors: Ying Pang, Lili Liu, Shuainan Wu, Jianqi Wang, Lu Liu
Format: Article
Language:English
Published: Wiley 2023-07-01
Series:Immunity, Inflammation and Disease
Subjects:
Online Access:https://doi.org/10.1002/iid3.880
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author Ying Pang
Lili Liu
Shuainan Wu
Jianqi Wang
Lu Liu
author_facet Ying Pang
Lili Liu
Shuainan Wu
Jianqi Wang
Lu Liu
author_sort Ying Pang
collection DOAJ
description Abstract Introduction Inflammasome and pyroptosis play important roles in periodontitis. Gasdermin D (GSDMD), a key factor in pyroptosis, is cleaved by caspase‐1 and regulated by ubiquitination. Synoviolin is a ubiquitin E3 ligase that interacts with GSDMD. In this study, the effects of Synoviolin on inflammasome activation and periodontitis were explored. Methods The expression of IL‐1β, GSDMD, and Synoviolin in peripheral blood mononuclear cells from patients with periodontitis was determined. The interaction between GSDMD and Synoviolin was studied. The cytokine level in gingival tissues and the distance from the cementoenamel junction to the alveolar bone crest were measured in mice with Synoviolin deficiency in myeloid cells. Results We reported that elevated mRNA and protein levels of IL‐1β and GSDMD, decreased levels of Synoviolin mRNA and protein, and decreased ubiquitination of GSDMD were associated with periodontitis. Synoviolin interacted with GSDMD. Synoviolin‐deficient bone marrow‐derived macrophages had increased IL‐1β and IL‐18 secretion after ATP stimulation. Mice with Synoviolin deficiency in myeloid cells had more severe periodontitis and upregulated IL‐1β and IL‐18. Conclusions Therefore, we conclude that Synoviolin suppresses inflammasome activation and periodontitis by regulating GSDMD stability.
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spelling doaj.art-5697a30aad5e488fa53108a54db8f0c92023-07-28T17:22:31ZengWileyImmunity, Inflammation and Disease2050-45272023-07-01117n/an/a10.1002/iid3.880Synoviolin alleviates GSDMD‐mediated periodontitis by suppressing its stabilityYing Pang0Lili Liu1Shuainan Wu2Jianqi Wang3Lu Liu4Dental Clinic, Cangzhou Central Hospital Cangzhou Hebei People's Republic of ChinaDental Clinic, Cangzhou Central Hospital Cangzhou Hebei People's Republic of ChinaDental Clinic, Cangzhou Central Hospital Cangzhou Hebei People's Republic of ChinaDental Clinic, Cangzhou Central Hospital Cangzhou Hebei People's Republic of ChinaDental Clinic, Cangzhou Central Hospital Cangzhou Hebei People's Republic of ChinaAbstract Introduction Inflammasome and pyroptosis play important roles in periodontitis. Gasdermin D (GSDMD), a key factor in pyroptosis, is cleaved by caspase‐1 and regulated by ubiquitination. Synoviolin is a ubiquitin E3 ligase that interacts with GSDMD. In this study, the effects of Synoviolin on inflammasome activation and periodontitis were explored. Methods The expression of IL‐1β, GSDMD, and Synoviolin in peripheral blood mononuclear cells from patients with periodontitis was determined. The interaction between GSDMD and Synoviolin was studied. The cytokine level in gingival tissues and the distance from the cementoenamel junction to the alveolar bone crest were measured in mice with Synoviolin deficiency in myeloid cells. Results We reported that elevated mRNA and protein levels of IL‐1β and GSDMD, decreased levels of Synoviolin mRNA and protein, and decreased ubiquitination of GSDMD were associated with periodontitis. Synoviolin interacted with GSDMD. Synoviolin‐deficient bone marrow‐derived macrophages had increased IL‐1β and IL‐18 secretion after ATP stimulation. Mice with Synoviolin deficiency in myeloid cells had more severe periodontitis and upregulated IL‐1β and IL‐18. Conclusions Therefore, we conclude that Synoviolin suppresses inflammasome activation and periodontitis by regulating GSDMD stability.https://doi.org/10.1002/iid3.880GSDMDinflammasomeperiodontitisSynoviolin
spellingShingle Ying Pang
Lili Liu
Shuainan Wu
Jianqi Wang
Lu Liu
Synoviolin alleviates GSDMD‐mediated periodontitis by suppressing its stability
Immunity, Inflammation and Disease
GSDMD
inflammasome
periodontitis
Synoviolin
title Synoviolin alleviates GSDMD‐mediated periodontitis by suppressing its stability
title_full Synoviolin alleviates GSDMD‐mediated periodontitis by suppressing its stability
title_fullStr Synoviolin alleviates GSDMD‐mediated periodontitis by suppressing its stability
title_full_unstemmed Synoviolin alleviates GSDMD‐mediated periodontitis by suppressing its stability
title_short Synoviolin alleviates GSDMD‐mediated periodontitis by suppressing its stability
title_sort synoviolin alleviates gsdmd mediated periodontitis by suppressing its stability
topic GSDMD
inflammasome
periodontitis
Synoviolin
url https://doi.org/10.1002/iid3.880
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AT shuainanwu synoviolinalleviatesgsdmdmediatedperiodontitisbysuppressingitsstability
AT jianqiwang synoviolinalleviatesgsdmdmediatedperiodontitisbysuppressingitsstability
AT luliu synoviolinalleviatesgsdmdmediatedperiodontitisbysuppressingitsstability