SARS-CoV-2 spike protein promotes inflammatory cytokine activation and aggravates rheumatoid arthritis
Abstract Background Coronavirus disease 2019 (COVID-19) induces inflammation, autoantibody production, and thrombosis, which are common symptoms of autoimmune diseases, including rheumatoid arthritis (RA). However, the effect of COVID-19 on autoimmune disease is not yet fully understood. Methods Thi...
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| Format: | Article |
| Language: | English |
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BMC
2023-03-01
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| Series: | Cell Communication and Signaling |
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| Online Access: | https://doi.org/10.1186/s12964-023-01044-0 |
| _version_ | 1797864044678348800 |
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| author | A Ram Lee Jin Seok Woo Seon-Yeong Lee Yeon Su Lee Jooyeon Jung Chae Rim Lee Sung-Hwan Park Mi-La Cho |
| author_facet | A Ram Lee Jin Seok Woo Seon-Yeong Lee Yeon Su Lee Jooyeon Jung Chae Rim Lee Sung-Hwan Park Mi-La Cho |
| author_sort | A Ram Lee |
| collection | DOAJ |
| description | Abstract Background Coronavirus disease 2019 (COVID-19) induces inflammation, autoantibody production, and thrombosis, which are common symptoms of autoimmune diseases, including rheumatoid arthritis (RA). However, the effect of COVID-19 on autoimmune disease is not yet fully understood. Methods This study was performed to investigate the effects of COVID-19 on the development and progression of RA using a collagen-induced arthritis (CIA) animal model. Human fibroblast-like synoviocytes (FLS) were transduced with lentivirus carrying the SARS-CoV-2 spike protein gene in vitro, and the levels of inflammatory cytokine and chemokine expression were measured. For in vivo experiments, CIA mice were injected with the gene encoding SARS-CoV-2 spike protein, and disease severity, levels of autoantibodies, thrombotic factors, and inflammatory cytokine and chemokine expression were assessed. In the in vitro experiments, the levels of inflammatory cytokine and chemokine expression were significantly increased by overexpression of SARS-CoV-2 spike protein in human FLS. Results The incidence and severity of RA in CIA mice were slightly increased by SARS-CoV-2 spike protein in vivo. In addition, the levels of autoantibodies and thrombotic factors, such as anti-CXC chemokine ligand 4 (CXCL4, also called PF4) antibodies and anti-phospholipid antibodies were significantly increased by SARS-CoV-2 spike protein. Furthermore, tissue destruction and inflammatory cytokine level in joint tissue were markedly increased in CIA mice by SARS-CoV-2 spike protein. Conclusions The results of the present study suggested that COVID-19 accelerates the development and progression of RA by increasing inflammation, autoantibody production, and thrombosis. Video Abstract |
| first_indexed | 2024-04-09T22:46:19Z |
| format | Article |
| id | doaj.art-d082d80c8f4641978627b34b4519b8cc |
| institution | Directory Open Access Journal |
| issn | 1478-811X |
| language | English |
| last_indexed | 2024-04-09T22:46:19Z |
| publishDate | 2023-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj.art-d082d80c8f4641978627b34b4519b8cc2023-03-22T11:53:15ZengBMCCell Communication and Signaling1478-811X2023-03-012111810.1186/s12964-023-01044-0SARS-CoV-2 spike protein promotes inflammatory cytokine activation and aggravates rheumatoid arthritisA Ram Lee0Jin Seok Woo1Seon-Yeong Lee2Yeon Su Lee3Jooyeon Jung4Chae Rim Lee5Sung-Hwan Park6Mi-La Cho7Rheumatism Research Center, College of Medicine, Catholic Research Institute of Medical Science, The Catholic University of KoreaRheumatism Research Center, College of Medicine, Catholic Research Institute of Medical Science, The Catholic University of KoreaRheumatism Research Center, College of Medicine, Catholic Research Institute of Medical Science, The Catholic University of KoreaRheumatism Research Center, College of Medicine, Catholic Research Institute of Medical Science, The Catholic University of KoreaRheumatism Research Center, College of Medicine, Catholic Research Institute of Medical Science, The Catholic University of KoreaRheumatism Research Center, College of Medicine, Catholic Research Institute of Medical Science, The Catholic University of KoreaDivision of Rheumatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of KoreaRheumatism Research Center, College of Medicine, Catholic Research Institute of Medical Science, The Catholic University of KoreaAbstract Background Coronavirus disease 2019 (COVID-19) induces inflammation, autoantibody production, and thrombosis, which are common symptoms of autoimmune diseases, including rheumatoid arthritis (RA). However, the effect of COVID-19 on autoimmune disease is not yet fully understood. Methods This study was performed to investigate the effects of COVID-19 on the development and progression of RA using a collagen-induced arthritis (CIA) animal model. Human fibroblast-like synoviocytes (FLS) were transduced with lentivirus carrying the SARS-CoV-2 spike protein gene in vitro, and the levels of inflammatory cytokine and chemokine expression were measured. For in vivo experiments, CIA mice were injected with the gene encoding SARS-CoV-2 spike protein, and disease severity, levels of autoantibodies, thrombotic factors, and inflammatory cytokine and chemokine expression were assessed. In the in vitro experiments, the levels of inflammatory cytokine and chemokine expression were significantly increased by overexpression of SARS-CoV-2 spike protein in human FLS. Results The incidence and severity of RA in CIA mice were slightly increased by SARS-CoV-2 spike protein in vivo. In addition, the levels of autoantibodies and thrombotic factors, such as anti-CXC chemokine ligand 4 (CXCL4, also called PF4) antibodies and anti-phospholipid antibodies were significantly increased by SARS-CoV-2 spike protein. Furthermore, tissue destruction and inflammatory cytokine level in joint tissue were markedly increased in CIA mice by SARS-CoV-2 spike protein. Conclusions The results of the present study suggested that COVID-19 accelerates the development and progression of RA by increasing inflammation, autoantibody production, and thrombosis. Video Abstracthttps://doi.org/10.1186/s12964-023-01044-0Coronavirus disease 2019 (COVID-19)Autoimmune diseaseRheumatoid arthritis (RA)InflammationThrombosis |
| spellingShingle | A Ram Lee Jin Seok Woo Seon-Yeong Lee Yeon Su Lee Jooyeon Jung Chae Rim Lee Sung-Hwan Park Mi-La Cho SARS-CoV-2 spike protein promotes inflammatory cytokine activation and aggravates rheumatoid arthritis Cell Communication and Signaling Coronavirus disease 2019 (COVID-19) Autoimmune disease Rheumatoid arthritis (RA) Inflammation Thrombosis |
| title | SARS-CoV-2 spike protein promotes inflammatory cytokine activation and aggravates rheumatoid arthritis |
| title_full | SARS-CoV-2 spike protein promotes inflammatory cytokine activation and aggravates rheumatoid arthritis |
| title_fullStr | SARS-CoV-2 spike protein promotes inflammatory cytokine activation and aggravates rheumatoid arthritis |
| title_full_unstemmed | SARS-CoV-2 spike protein promotes inflammatory cytokine activation and aggravates rheumatoid arthritis |
| title_short | SARS-CoV-2 spike protein promotes inflammatory cytokine activation and aggravates rheumatoid arthritis |
| title_sort | sars cov 2 spike protein promotes inflammatory cytokine activation and aggravates rheumatoid arthritis |
| topic | Coronavirus disease 2019 (COVID-19) Autoimmune disease Rheumatoid arthritis (RA) Inflammation Thrombosis |
| url | https://doi.org/10.1186/s12964-023-01044-0 |
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