The roles of neutrophil serine proteinases in idiopathic inflammatory myopathies
Abstract Background Dermatomyositis and polymyositis are the best known idiopathic inflammatory myopathies (IIMs). Classic histopathologic findings include the infiltration of inflammatory cells into muscle tissues. Neutrophil serine proteinases (NSPs) are granule-associated enzymes and play roles i...
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| Format: | Article |
| Language: | English |
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BMC
2018-07-01
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| Series: | Arthritis Research & Therapy |
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| Online Access: | http://link.springer.com/article/10.1186/s13075-018-1632-x |
| _version_ | 1811267310643576832 |
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| author | Siming Gao Xiaoxia Zuo Di Liu Yizhi Xiao Honglin Zhu Huali Zhang Hui Luo |
| author_facet | Siming Gao Xiaoxia Zuo Di Liu Yizhi Xiao Honglin Zhu Huali Zhang Hui Luo |
| author_sort | Siming Gao |
| collection | DOAJ |
| description | Abstract Background Dermatomyositis and polymyositis are the best known idiopathic inflammatory myopathies (IIMs). Classic histopathologic findings include the infiltration of inflammatory cells into muscle tissues. Neutrophil serine proteinases (NSPs) are granule-associated enzymes and play roles in inflammatory cell migration by increasing the permeability of vascular endothelial cells. In this study, we aimed to find the roles of NSPs in pathogenesis of IIMs. Methods RNA and DNA were isolated to measure the relative expression of NSPs and their methylation levels. The expression of NSPs in serum and muscle tissues was tested by enzyme-linked immunosorbent assay, immunohistochemistry, and immunofluorescence, respectively. Serum from patients was used to culture the human dermal microvascular endothelial cells (HDMECs), and then we observed the influence of serum on expression of VE-cadherin, endothelial cell tube formation, and transendothelial migration of peripheral blood mononuclear cells (PBMCs). Results We found that the expression of NSPs was increased in PBMCs, serum, and muscle tissues of IIM patients; these NSPs were hypomethylated in the PBMCs of patients. Serum NSPs were positively correlated with clinical indicators of IIM patients, including lactic dehydrogenase, erythrocyte sedimentation rate, C-reactive protein, immunoglobulin G, immunoglobulin M, and immunoglobulin A. Patients with anti-Jo-1, with anti-Ro-52, or without interstitial lung disease had lower levels of proteinase 3. Serum NSPs degraded the VE-cadherin of HDMECs, and serum NSP application increased the permeability of HDMECs. Conclusions Our studies indicate, for the first time, that NSPs play an important role in muscle inflammatory cell infiltration by increasing the permeability of vascular endothelial cells in IIM patients. |
| first_indexed | 2024-04-12T21:00:22Z |
| format | Article |
| id | doaj.art-6364779e88f64605a63863878b0fe9fd |
| institution | Directory Open Access Journal |
| issn | 1478-6362 |
| language | English |
| last_indexed | 2024-04-12T21:00:22Z |
| publishDate | 2018-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Arthritis Research & Therapy |
| spelling | doaj.art-6364779e88f64605a63863878b0fe9fd2022-12-22T03:16:52ZengBMCArthritis Research & Therapy1478-63622018-07-0120111010.1186/s13075-018-1632-xThe roles of neutrophil serine proteinases in idiopathic inflammatory myopathiesSiming Gao0Xiaoxia Zuo1Di Liu2Yizhi Xiao3Honglin Zhu4Huali Zhang5Hui Luo6Department of Rheumatology, Xiangya Hospital, Central South UniversityDepartment of Rheumatology, Xiangya Hospital, Central South UniversityDepartment of Rheumatology, Xiangya Hospital, Central South UniversityDepartment of Rheumatology, Xiangya Hospital, Central South UniversityDepartment of Rheumatology, Xiangya Hospital, Central South UniversityDepartment of Pathophysiology, Xiangya School of Medicine, Central South UniversityDepartment of Rheumatology, Xiangya Hospital, Central South UniversityAbstract Background Dermatomyositis and polymyositis are the best known idiopathic inflammatory myopathies (IIMs). Classic histopathologic findings include the infiltration of inflammatory cells into muscle tissues. Neutrophil serine proteinases (NSPs) are granule-associated enzymes and play roles in inflammatory cell migration by increasing the permeability of vascular endothelial cells. In this study, we aimed to find the roles of NSPs in pathogenesis of IIMs. Methods RNA and DNA were isolated to measure the relative expression of NSPs and their methylation levels. The expression of NSPs in serum and muscle tissues was tested by enzyme-linked immunosorbent assay, immunohistochemistry, and immunofluorescence, respectively. Serum from patients was used to culture the human dermal microvascular endothelial cells (HDMECs), and then we observed the influence of serum on expression of VE-cadherin, endothelial cell tube formation, and transendothelial migration of peripheral blood mononuclear cells (PBMCs). Results We found that the expression of NSPs was increased in PBMCs, serum, and muscle tissues of IIM patients; these NSPs were hypomethylated in the PBMCs of patients. Serum NSPs were positively correlated with clinical indicators of IIM patients, including lactic dehydrogenase, erythrocyte sedimentation rate, C-reactive protein, immunoglobulin G, immunoglobulin M, and immunoglobulin A. Patients with anti-Jo-1, with anti-Ro-52, or without interstitial lung disease had lower levels of proteinase 3. Serum NSPs degraded the VE-cadherin of HDMECs, and serum NSP application increased the permeability of HDMECs. Conclusions Our studies indicate, for the first time, that NSPs play an important role in muscle inflammatory cell infiltration by increasing the permeability of vascular endothelial cells in IIM patients.http://link.springer.com/article/10.1186/s13075-018-1632-xDermatomyositisPolymyositisNeutrophil serine proteinasesVascular permeabilityInflammatory cell migration |
| spellingShingle | Siming Gao Xiaoxia Zuo Di Liu Yizhi Xiao Honglin Zhu Huali Zhang Hui Luo The roles of neutrophil serine proteinases in idiopathic inflammatory myopathies Arthritis Research & Therapy Dermatomyositis Polymyositis Neutrophil serine proteinases Vascular permeability Inflammatory cell migration |
| title | The roles of neutrophil serine proteinases in idiopathic inflammatory myopathies |
| title_full | The roles of neutrophil serine proteinases in idiopathic inflammatory myopathies |
| title_fullStr | The roles of neutrophil serine proteinases in idiopathic inflammatory myopathies |
| title_full_unstemmed | The roles of neutrophil serine proteinases in idiopathic inflammatory myopathies |
| title_short | The roles of neutrophil serine proteinases in idiopathic inflammatory myopathies |
| title_sort | roles of neutrophil serine proteinases in idiopathic inflammatory myopathies |
| topic | Dermatomyositis Polymyositis Neutrophil serine proteinases Vascular permeability Inflammatory cell migration |
| url | http://link.springer.com/article/10.1186/s13075-018-1632-x |
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