SARS Unique Domain (SUD) of Severe Acute Respiratory Syndrome Coronavirus Induces NLRP3 Inflammasome-Dependent CXCL10-Mediated Pulmonary Inflammation
Severe acute respiratory syndrome–associated coronavirus (SARS-CoV) initiates the cytokine/chemokine storm-mediated lung injury. The SARS-CoV unique domain (SUD) with three macrodomains (N, M, and C), showing the G-quadruplex binding activity, was examined the possible role in SARS pathogenesis in t...
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MDPI AG
2020-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/9/3179 |
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| author | Young-Sheng Chang Bo-Han Ko Jyh-Cherng Ju Hsin-Hou Chang Su-Hua Huang Cheng-Wen Lin |
| author_facet | Young-Sheng Chang Bo-Han Ko Jyh-Cherng Ju Hsin-Hou Chang Su-Hua Huang Cheng-Wen Lin |
| author_sort | Young-Sheng Chang |
| collection | DOAJ |
| description | Severe acute respiratory syndrome–associated coronavirus (SARS-CoV) initiates the cytokine/chemokine storm-mediated lung injury. The SARS-CoV unique domain (SUD) with three macrodomains (N, M, and C), showing the G-quadruplex binding activity, was examined the possible role in SARS pathogenesis in this study. The chemokine profile analysis indicated that SARS-CoV SUD significantly up-regulated the expression of CXCL10, CCL5 and interleukin (IL)-1β in human lung epithelial cells and in the lung tissues of the mice intratracheally instilled with the recombinant plasmids. Among the SUD subdomains, SUD-MC substantially activated AP-1-mediated CXCL10 expression in vitro. In the wild type mice, SARS-CoV SUD-MC triggered the pulmonary infiltration of macrophages and monocytes, inducing CXCL10-mediated inflammatory responses and severe diffuse alveolar damage symptoms. Moreover, SUD-MC actuated NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome-dependent pulmonary inflammation, as confirmed by the NLRP3 inflammasome inhibitor and the NLRP3<sup>−/−</sup> mouse model. This study demonstrated that SARS-CoV SUD modulated NLRP3 inflammasome-dependent CXCL10-mediated pulmonary inflammation, providing the potential therapeutic targets for developing the antiviral agents. |
| first_indexed | 2024-03-10T20:07:21Z |
| format | Article |
| id | doaj.art-4f8a2e7dccd243a1a4e5435ebaa4101d |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T20:07:21Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-4f8a2e7dccd243a1a4e5435ebaa4101d2023-11-19T23:09:27ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-04-01219317910.3390/ijms21093179SARS Unique Domain (SUD) of Severe Acute Respiratory Syndrome Coronavirus Induces NLRP3 Inflammasome-Dependent CXCL10-Mediated Pulmonary InflammationYoung-Sheng Chang0Bo-Han Ko1Jyh-Cherng Ju2Hsin-Hou Chang3Su-Hua Huang4Cheng-Wen Lin5Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 404394, TaiwanDepartment of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 404394, TaiwanGraduate Institute of Biomedical Sciences, China Medical University, Taichung 404394, TaiwanDepartment of Molecular Biology and Human Genetics, Tzu Chi University, Hualien 970301, TaiwanDepartment of Biotechnology, Asia University, Wufeng, Taichung 413305, TaiwanDepartment of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 404394, TaiwanSevere acute respiratory syndrome–associated coronavirus (SARS-CoV) initiates the cytokine/chemokine storm-mediated lung injury. The SARS-CoV unique domain (SUD) with three macrodomains (N, M, and C), showing the G-quadruplex binding activity, was examined the possible role in SARS pathogenesis in this study. The chemokine profile analysis indicated that SARS-CoV SUD significantly up-regulated the expression of CXCL10, CCL5 and interleukin (IL)-1β in human lung epithelial cells and in the lung tissues of the mice intratracheally instilled with the recombinant plasmids. Among the SUD subdomains, SUD-MC substantially activated AP-1-mediated CXCL10 expression in vitro. In the wild type mice, SARS-CoV SUD-MC triggered the pulmonary infiltration of macrophages and monocytes, inducing CXCL10-mediated inflammatory responses and severe diffuse alveolar damage symptoms. Moreover, SUD-MC actuated NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome-dependent pulmonary inflammation, as confirmed by the NLRP3 inflammasome inhibitor and the NLRP3<sup>−/−</sup> mouse model. This study demonstrated that SARS-CoV SUD modulated NLRP3 inflammasome-dependent CXCL10-mediated pulmonary inflammation, providing the potential therapeutic targets for developing the antiviral agents.https://www.mdpi.com/1422-0067/21/9/3179SARS-coronavirusSARS-CoV unique domain (SUD), CXCL10NLRP3 inflammasomepulmonary inflammation |
| spellingShingle | Young-Sheng Chang Bo-Han Ko Jyh-Cherng Ju Hsin-Hou Chang Su-Hua Huang Cheng-Wen Lin SARS Unique Domain (SUD) of Severe Acute Respiratory Syndrome Coronavirus Induces NLRP3 Inflammasome-Dependent CXCL10-Mediated Pulmonary Inflammation International Journal of Molecular Sciences SARS-coronavirus SARS-CoV unique domain (SUD), CXCL10 NLRP3 inflammasome pulmonary inflammation |
| title | SARS Unique Domain (SUD) of Severe Acute Respiratory Syndrome Coronavirus Induces NLRP3 Inflammasome-Dependent CXCL10-Mediated Pulmonary Inflammation |
| title_full | SARS Unique Domain (SUD) of Severe Acute Respiratory Syndrome Coronavirus Induces NLRP3 Inflammasome-Dependent CXCL10-Mediated Pulmonary Inflammation |
| title_fullStr | SARS Unique Domain (SUD) of Severe Acute Respiratory Syndrome Coronavirus Induces NLRP3 Inflammasome-Dependent CXCL10-Mediated Pulmonary Inflammation |
| title_full_unstemmed | SARS Unique Domain (SUD) of Severe Acute Respiratory Syndrome Coronavirus Induces NLRP3 Inflammasome-Dependent CXCL10-Mediated Pulmonary Inflammation |
| title_short | SARS Unique Domain (SUD) of Severe Acute Respiratory Syndrome Coronavirus Induces NLRP3 Inflammasome-Dependent CXCL10-Mediated Pulmonary Inflammation |
| title_sort | sars unique domain sud of severe acute respiratory syndrome coronavirus induces nlrp3 inflammasome dependent cxcl10 mediated pulmonary inflammation |
| topic | SARS-coronavirus SARS-CoV unique domain (SUD), CXCL10 NLRP3 inflammasome pulmonary inflammation |
| url | https://www.mdpi.com/1422-0067/21/9/3179 |
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