Soluble egg antigen of Schistosoma japonicum induces pyroptosis in hepatic stellate cells by modulating ROS production
Abstract Background Inflammation-induced dysfunction of hepatic stellate cells (HSCs) is involved in schistosomiasis-associated liver fibrosis, and soluble egg antigen (SEA) is a crucial pathogen-associated molecular pattern associated with liver injury in schistosomiasis. In addition, numerous stud...
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| Format: | Article |
| Language: | English |
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BMC
2019-10-01
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| Series: | Parasites & Vectors |
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| Online Access: | http://link.springer.com/article/10.1186/s13071-019-3729-8 |
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| author | De-Long Kong Fan-Yun Kong Xiang-Ye Liu Chao Yan Jie Cui Ren-Xian Tang Kui-Yang Zheng |
| author_facet | De-Long Kong Fan-Yun Kong Xiang-Ye Liu Chao Yan Jie Cui Ren-Xian Tang Kui-Yang Zheng |
| author_sort | De-Long Kong |
| collection | DOAJ |
| description | Abstract Background Inflammation-induced dysfunction of hepatic stellate cells (HSCs) is involved in schistosomiasis-associated liver fibrosis, and soluble egg antigen (SEA) is a crucial pathogen-associated molecular pattern associated with liver injury in schistosomiasis. In addition, numerous studies have shown that caspase-1-mediated pyroptosis participates in the development of multiple inflammation-related diseases. However, whether pyroptotic cell death of HSCs is involved in SEA-mediated liver damage is not well understood. Methods Primary cultured HSCs and Schistosoma japonicum-infected mouse liver tissue were analysed for histological changes and caspase-1 activation, and the role of pyroptosis in the mechanisms underlying SEA-induced HSC death was investigated. Accumulation of reactive oxygen species (ROS) in infected livers and SEA-stimulated HSCs was measured by flow cytometry and immunofluorescence. Results Caspase-1 activity was elevated in both liver tissues and HSCs of S. japonicum-infected mice. Furthermore, SEA stimulation increased the proportion of pyroptotic HSCs, as shown by lactate dehydrogenase (LDH) release assays and by flow cytometric analysis of propidium iodide (PI) and caspase-1 double staining in cells. In addition, ROS generation was elevated in infected liver tissues and SEA-stimulated HSCs, and ROS inhibition downregulated SEA-induced caspase-1 activation and pyroptosis in HSCs. Conclusions Our present study demonstrates that pyroptotic cell death in HSCs induced by SEA via ROS-mediated caspase-1 activation may serve as a significant mechanism to initiate the inflammatory response and thereby exacerbate liver injury during S. japonicum infection. |
| first_indexed | 2024-12-24T10:02:40Z |
| format | Article |
| id | doaj.art-e7d677042de14699b1bb700a5540915e |
| institution | Directory Open Access Journal |
| issn | 1756-3305 |
| language | English |
| last_indexed | 2024-12-24T10:02:40Z |
| publishDate | 2019-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Parasites & Vectors |
| spelling | doaj.art-e7d677042de14699b1bb700a5540915e2022-12-21T17:01:00ZengBMCParasites & Vectors1756-33052019-10-0112111210.1186/s13071-019-3729-8Soluble egg antigen of Schistosoma japonicum induces pyroptosis in hepatic stellate cells by modulating ROS productionDe-Long Kong0Fan-Yun Kong1Xiang-Ye Liu2Chao Yan3Jie Cui4Ren-Xian Tang5Kui-Yang Zheng6Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Laboratory of Infection and Immunity, Xuzhou Medical UniversityJiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Laboratory of Infection and Immunity, Xuzhou Medical UniversityJiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Laboratory of Infection and Immunity, Xuzhou Medical UniversityJiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Laboratory of Infection and Immunity, Xuzhou Medical UniversityDepartment of Physiology, Xuzhou Medical UniversityJiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Laboratory of Infection and Immunity, Xuzhou Medical UniversityJiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Laboratory of Infection and Immunity, Xuzhou Medical UniversityAbstract Background Inflammation-induced dysfunction of hepatic stellate cells (HSCs) is involved in schistosomiasis-associated liver fibrosis, and soluble egg antigen (SEA) is a crucial pathogen-associated molecular pattern associated with liver injury in schistosomiasis. In addition, numerous studies have shown that caspase-1-mediated pyroptosis participates in the development of multiple inflammation-related diseases. However, whether pyroptotic cell death of HSCs is involved in SEA-mediated liver damage is not well understood. Methods Primary cultured HSCs and Schistosoma japonicum-infected mouse liver tissue were analysed for histological changes and caspase-1 activation, and the role of pyroptosis in the mechanisms underlying SEA-induced HSC death was investigated. Accumulation of reactive oxygen species (ROS) in infected livers and SEA-stimulated HSCs was measured by flow cytometry and immunofluorescence. Results Caspase-1 activity was elevated in both liver tissues and HSCs of S. japonicum-infected mice. Furthermore, SEA stimulation increased the proportion of pyroptotic HSCs, as shown by lactate dehydrogenase (LDH) release assays and by flow cytometric analysis of propidium iodide (PI) and caspase-1 double staining in cells. In addition, ROS generation was elevated in infected liver tissues and SEA-stimulated HSCs, and ROS inhibition downregulated SEA-induced caspase-1 activation and pyroptosis in HSCs. Conclusions Our present study demonstrates that pyroptotic cell death in HSCs induced by SEA via ROS-mediated caspase-1 activation may serve as a significant mechanism to initiate the inflammatory response and thereby exacerbate liver injury during S. japonicum infection.http://link.springer.com/article/10.1186/s13071-019-3729-8SchistosomiasisLiver fibrosisPyroptosisROS |
| spellingShingle | De-Long Kong Fan-Yun Kong Xiang-Ye Liu Chao Yan Jie Cui Ren-Xian Tang Kui-Yang Zheng Soluble egg antigen of Schistosoma japonicum induces pyroptosis in hepatic stellate cells by modulating ROS production Parasites & Vectors Schistosomiasis Liver fibrosis Pyroptosis ROS |
| title | Soluble egg antigen of Schistosoma japonicum induces pyroptosis in hepatic stellate cells by modulating ROS production |
| title_full | Soluble egg antigen of Schistosoma japonicum induces pyroptosis in hepatic stellate cells by modulating ROS production |
| title_fullStr | Soluble egg antigen of Schistosoma japonicum induces pyroptosis in hepatic stellate cells by modulating ROS production |
| title_full_unstemmed | Soluble egg antigen of Schistosoma japonicum induces pyroptosis in hepatic stellate cells by modulating ROS production |
| title_short | Soluble egg antigen of Schistosoma japonicum induces pyroptosis in hepatic stellate cells by modulating ROS production |
| title_sort | soluble egg antigen of schistosoma japonicum induces pyroptosis in hepatic stellate cells by modulating ros production |
| topic | Schistosomiasis Liver fibrosis Pyroptosis ROS |
| url | http://link.springer.com/article/10.1186/s13071-019-3729-8 |
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