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Synoviolin alleviates GSDMD‐mediated periodontitis by suppressing its stability
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 inflam...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10336677/ https://www.ncbi.nlm.nih.gov/pubmed/37506160 http://dx.doi.org/10.1002/iid3.880 |
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author | Pang, Ying Liu, Lili Wu, Shuainan Wang, Jianqi Liu, Lu |
author_facet | Pang, Ying Liu, Lili Wu, Shuainan Wang, Jianqi Liu, Lu |
author_sort | Pang, Ying |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10336677 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-103366772023-07-13 Synoviolin alleviates GSDMD‐mediated periodontitis by suppressing its stability Pang, Ying Liu, Lili Wu, Shuainan Wang, Jianqi Liu, Lu Immun Inflamm Dis Original Articles 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. John Wiley and Sons Inc. 2023-07-12 /pmc/articles/PMC10336677/ /pubmed/37506160 http://dx.doi.org/10.1002/iid3.880 Text en © 2023 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Pang, Ying Liu, Lili Wu, Shuainan Wang, Jianqi Liu, Lu Synoviolin alleviates GSDMD‐mediated periodontitis by suppressing its stability |
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 | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10336677/ https://www.ncbi.nlm.nih.gov/pubmed/37506160 http://dx.doi.org/10.1002/iid3.880 |
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