Downregulation of BIRC2 hinders the progression of rheumatoid arthritis through regulating TRADD
Abstract Aim Rheumatoid arthritis (RA) is a chronic inflammation mediated by an autoimmune response. Baculoviral IAP repeat‐containing 2 (BIRC2) and tumor necrosis factor receptor 1‐associated death domain protein (TRADD) have been reported to be highly expressed in RA, while their specific roles du...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-10-01
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| Series: | Immunity, Inflammation and Disease |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/iid3.978 |
| _version_ | 1797641956572004352 |
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| author | Yanting Rao Shengjing Xu Ting Lu Yuanyuan Wang Manman Liu Wei Zhang |
| author_facet | Yanting Rao Shengjing Xu Ting Lu Yuanyuan Wang Manman Liu Wei Zhang |
| author_sort | Yanting Rao |
| collection | DOAJ |
| description | Abstract Aim Rheumatoid arthritis (RA) is a chronic inflammation mediated by an autoimmune response. Baculoviral IAP repeat‐containing 2 (BIRC2) and tumor necrosis factor receptor 1‐associated death domain protein (TRADD) have been reported to be highly expressed in RA, while their specific roles during RA progression remain unclear. This study aims to explore the specific regulation of BIRC2/TRADD during the progression of RA. Methods C28/I2 cells were stimulated by lipopolysaccharide (LPS) to establish an in vitro RA cellular model. The expression level of BIRC2 and TRADD was examined by quantitative real‐time polymerase chain reaction and western blot. Cell Counting Kit‐8 and flow cytometry assays were performed to examine cell viability and necroptosis, respectively. The oxidative stress markers were detected using commercial kits, and the pro‐inflammatory cytokines were measured by ELISA assay. The interaction between BIRC2 and TRADD was verified by co‐immunoprecipitation assay. Results BIRC2 and TRADD were discovered to be highly expressed in LPS‐mediated C28/I2 cells. BIRC2 knockdown was demonstrated to inhibit LPS‐induced cell viability loss, necroptosis, oxidative stress, and inflammation in C28/I2 cells. BIRC2 could interact with TRADD and positively regulate TRADD expression. In addition, the protective role of BIRC2 knockdown against LPS‐mediated injuries in C28/I2 cells was partly weakened by TRADD overexpression. Conclusion In summary, BIRC2 knockdown alleviated necroptosis, oxidative stress, and inflammation in LPS‐mediated C28/I2 cells, which might correlate to the regulatory role of TRADD, indicating a novel target for the treatment of RA. |
| first_indexed | 2024-03-11T13:53:12Z |
| format | Article |
| id | doaj.art-5ad9470273fc44b49d0e3325338e6e92 |
| institution | Directory Open Access Journal |
| issn | 2050-4527 |
| language | English |
| last_indexed | 2024-03-11T13:53:12Z |
| publishDate | 2023-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Immunity, Inflammation and Disease |
| spelling | doaj.art-5ad9470273fc44b49d0e3325338e6e922023-11-02T07:56:18ZengWileyImmunity, Inflammation and Disease2050-45272023-10-011110n/an/a10.1002/iid3.978Downregulation of BIRC2 hinders the progression of rheumatoid arthritis through regulating TRADDYanting Rao0Shengjing Xu1Ting Lu2Yuanyuan Wang3Manman Liu4Wei Zhang5Department of Rheumatology and Immunology The Affiliated Jiangning Hospital of Nanjing Medical University Nanjing ChinaDepartment of Rheumatology and Immunology The Affiliated Jiangning Hospital of Nanjing Medical University Nanjing ChinaDepartment of Rheumatology and Immunology The Affiliated Jiangning Hospital of Nanjing Medical University Nanjing ChinaDepartment of Rheumatology and Immunology The Affiliated Jiangning Hospital of Nanjing Medical University Nanjing ChinaDepartment of Rheumatology and Immunology The Affiliated Jiangning Hospital of Nanjing Medical University Nanjing ChinaDepartment of Rheumatology and Immunology The Affiliated Jiangning Hospital of Nanjing Medical University Nanjing ChinaAbstract Aim Rheumatoid arthritis (RA) is a chronic inflammation mediated by an autoimmune response. Baculoviral IAP repeat‐containing 2 (BIRC2) and tumor necrosis factor receptor 1‐associated death domain protein (TRADD) have been reported to be highly expressed in RA, while their specific roles during RA progression remain unclear. This study aims to explore the specific regulation of BIRC2/TRADD during the progression of RA. Methods C28/I2 cells were stimulated by lipopolysaccharide (LPS) to establish an in vitro RA cellular model. The expression level of BIRC2 and TRADD was examined by quantitative real‐time polymerase chain reaction and western blot. Cell Counting Kit‐8 and flow cytometry assays were performed to examine cell viability and necroptosis, respectively. The oxidative stress markers were detected using commercial kits, and the pro‐inflammatory cytokines were measured by ELISA assay. The interaction between BIRC2 and TRADD was verified by co‐immunoprecipitation assay. Results BIRC2 and TRADD were discovered to be highly expressed in LPS‐mediated C28/I2 cells. BIRC2 knockdown was demonstrated to inhibit LPS‐induced cell viability loss, necroptosis, oxidative stress, and inflammation in C28/I2 cells. BIRC2 could interact with TRADD and positively regulate TRADD expression. In addition, the protective role of BIRC2 knockdown against LPS‐mediated injuries in C28/I2 cells was partly weakened by TRADD overexpression. Conclusion In summary, BIRC2 knockdown alleviated necroptosis, oxidative stress, and inflammation in LPS‐mediated C28/I2 cells, which might correlate to the regulatory role of TRADD, indicating a novel target for the treatment of RA.https://doi.org/10.1002/iid3.978BIRC2necroptosisrheumatoid arthritisTRADD |
| spellingShingle | Yanting Rao Shengjing Xu Ting Lu Yuanyuan Wang Manman Liu Wei Zhang Downregulation of BIRC2 hinders the progression of rheumatoid arthritis through regulating TRADD Immunity, Inflammation and Disease BIRC2 necroptosis rheumatoid arthritis TRADD |
| title | Downregulation of BIRC2 hinders the progression of rheumatoid arthritis through regulating TRADD |
| title_full | Downregulation of BIRC2 hinders the progression of rheumatoid arthritis through regulating TRADD |
| title_fullStr | Downregulation of BIRC2 hinders the progression of rheumatoid arthritis through regulating TRADD |
| title_full_unstemmed | Downregulation of BIRC2 hinders the progression of rheumatoid arthritis through regulating TRADD |
| title_short | Downregulation of BIRC2 hinders the progression of rheumatoid arthritis through regulating TRADD |
| title_sort | downregulation of birc2 hinders the progression of rheumatoid arthritis through regulating tradd |
| topic | BIRC2 necroptosis rheumatoid arthritis TRADD |
| url | https://doi.org/10.1002/iid3.978 |
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