PTX3 alleviates hard metal-induced acute lung injury through potentiating efferocytosis
Prolonged exposure to hard metal dust results in hard metal lung disease (HMLD) characterized by respiratory symptoms. Understanding the pathogenesis and pathological process of HMLD would be helpful for its early diagnosis and treatment. In this study, we established a mouse model of hard metal-ind...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-01-01
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| Series: | Ecotoxicology and Environmental Safety |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651321012513 |
| _version_ | 1819009857968144384 |
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| author | Weiwen Yan Dongyu Ma Yi Liu Wenqing Sun Demin Cheng Guanru Li Siyun Zhou Yue Wang Huanqiang Wang Chunhui Ni |
| author_facet | Weiwen Yan Dongyu Ma Yi Liu Wenqing Sun Demin Cheng Guanru Li Siyun Zhou Yue Wang Huanqiang Wang Chunhui Ni |
| author_sort | Weiwen Yan |
| collection | DOAJ |
| description | Prolonged exposure to hard metal dust results in hard metal lung disease (HMLD) characterized by respiratory symptoms. Understanding the pathogenesis and pathological process of HMLD would be helpful for its early diagnosis and treatment. In this study, we established a mouse model of hard metal-induced acute lung injury through one-time intratracheal instillation of WC-Co dust suspension. We found that WC-Co treatment damaged the lungs of mice, leading to increased production of IL-1β, TNF-α, IL-6 and IL-18, inflammatory cells infiltration and apoptosis. In vitro, WC-Co induced cytotoxicity, inflammatory response and apoptosis in macrophages (PMA-treated THP-1) and epithelial cells (A549) in a dose-dependent manner. Moreover, RNA-sequence and validation experiments verified that Pentraxin 3 (PTX3), an important mediator in the regulation of inflammation, was elevated both in vivo and in vitro induced by WC-Co. Functional experiments confirmed the PTX3, which was located on the membrane of apoptotic cells, promoted macrophage efferocytosis efficiently. This progress could help block the lung inflammation and contribute to the rapid recovery of WC-Co-induced acute lung injury. These observations provide a further understanding of the molecular mechanism of WC-Co-induced pulmonary injury and disclose PTX3 as a new potential therapeutic approach to relieve WC-Co-induced acute lung injury via efferocytosis. |
| first_indexed | 2024-12-21T01:03:02Z |
| format | Article |
| id | doaj.art-da06de4c1d6e46ccbd86f7ede593c630 |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-12-21T01:03:02Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-da06de4c1d6e46ccbd86f7ede593c6302022-12-21T19:21:08ZengElsevierEcotoxicology and Environmental Safety0147-65132022-01-01230113139PTX3 alleviates hard metal-induced acute lung injury through potentiating efferocytosisWeiwen Yan0Dongyu Ma1Yi Liu2Wenqing Sun3Demin Cheng4Guanru Li5Siyun Zhou6Yue Wang7Huanqiang Wang8Chunhui Ni9Center for Global Health, Key Laboratory of Modern Toxicology of Ministry of Education, Department of Occupational Medical and Environmental Health, School of Public Health, Nanjing Medical University, Nanjing 211166, ChinaCenter for Global Health, Key Laboratory of Modern Toxicology of Ministry of Education, Department of Occupational Medical and Environmental Health, School of Public Health, Nanjing Medical University, Nanjing 211166, ChinaGusu School, Nanjing Medical University, Nanjing 211166, ChinaCenter for Global Health, Key Laboratory of Modern Toxicology of Ministry of Education, Department of Occupational Medical and Environmental Health, School of Public Health, Nanjing Medical University, Nanjing 211166, ChinaCenter for Global Health, Key Laboratory of Modern Toxicology of Ministry of Education, Department of Occupational Medical and Environmental Health, School of Public Health, Nanjing Medical University, Nanjing 211166, ChinaCenter for Global Health, Key Laboratory of Modern Toxicology of Ministry of Education, Department of Occupational Medical and Environmental Health, School of Public Health, Nanjing Medical University, Nanjing 211166, ChinaCenter for Global Health, Key Laboratory of Modern Toxicology of Ministry of Education, Department of Occupational Medical and Environmental Health, School of Public Health, Nanjing Medical University, Nanjing 211166, ChinaCenter for Global Health, Key Laboratory of Modern Toxicology of Ministry of Education, Department of Occupational Medical and Environmental Health, School of Public Health, Nanjing Medical University, Nanjing 211166, ChinaNational Institute of Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, China; Corresponding authors.Center for Global Health, Key Laboratory of Modern Toxicology of Ministry of Education, Department of Occupational Medical and Environmental Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Corresponding authors.Prolonged exposure to hard metal dust results in hard metal lung disease (HMLD) characterized by respiratory symptoms. Understanding the pathogenesis and pathological process of HMLD would be helpful for its early diagnosis and treatment. In this study, we established a mouse model of hard metal-induced acute lung injury through one-time intratracheal instillation of WC-Co dust suspension. We found that WC-Co treatment damaged the lungs of mice, leading to increased production of IL-1β, TNF-α, IL-6 and IL-18, inflammatory cells infiltration and apoptosis. In vitro, WC-Co induced cytotoxicity, inflammatory response and apoptosis in macrophages (PMA-treated THP-1) and epithelial cells (A549) in a dose-dependent manner. Moreover, RNA-sequence and validation experiments verified that Pentraxin 3 (PTX3), an important mediator in the regulation of inflammation, was elevated both in vivo and in vitro induced by WC-Co. Functional experiments confirmed the PTX3, which was located on the membrane of apoptotic cells, promoted macrophage efferocytosis efficiently. This progress could help block the lung inflammation and contribute to the rapid recovery of WC-Co-induced acute lung injury. These observations provide a further understanding of the molecular mechanism of WC-Co-induced pulmonary injury and disclose PTX3 as a new potential therapeutic approach to relieve WC-Co-induced acute lung injury via efferocytosis.http://www.sciencedirect.com/science/article/pii/S0147651321012513Hard metal lung diseasePTX3ApoptosisEfferocytosisInflammation |
| spellingShingle | Weiwen Yan Dongyu Ma Yi Liu Wenqing Sun Demin Cheng Guanru Li Siyun Zhou Yue Wang Huanqiang Wang Chunhui Ni PTX3 alleviates hard metal-induced acute lung injury through potentiating efferocytosis Ecotoxicology and Environmental Safety Hard metal lung disease PTX3 Apoptosis Efferocytosis Inflammation |
| title | PTX3 alleviates hard metal-induced acute lung injury through potentiating efferocytosis |
| title_full | PTX3 alleviates hard metal-induced acute lung injury through potentiating efferocytosis |
| title_fullStr | PTX3 alleviates hard metal-induced acute lung injury through potentiating efferocytosis |
| title_full_unstemmed | PTX3 alleviates hard metal-induced acute lung injury through potentiating efferocytosis |
| title_short | PTX3 alleviates hard metal-induced acute lung injury through potentiating efferocytosis |
| title_sort | ptx3 alleviates hard metal induced acute lung injury through potentiating efferocytosis |
| topic | Hard metal lung disease PTX3 Apoptosis Efferocytosis Inflammation |
| url | http://www.sciencedirect.com/science/article/pii/S0147651321012513 |
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