C5a-C5aR1 axis mediates lung inflammation and fibrosis induced by single-walled carbon nanotubes via promoting neutrophils recruitment
A mounting number of studies have been documenting strong pro-inflammatory and pro-fibrotic effects of carbon nanotube (CNT). However, the molecular mechanisms of single-walled CNT (SWCNT)-provoked lung injury remain to be elucidated. Here, we established a mice model of SWCNT-induced lung injury by...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-01-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651324017032 |
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| author | Jiaojiao Zhu Xiang Zhang Lanlan Li Hongxu Yang Hang Liu Danyang Wu Zikai Liu Bin Liu Tong Shen |
| author_facet | Jiaojiao Zhu Xiang Zhang Lanlan Li Hongxu Yang Hang Liu Danyang Wu Zikai Liu Bin Liu Tong Shen |
| author_sort | Jiaojiao Zhu |
| collection | DOAJ |
| description | A mounting number of studies have been documenting strong pro-inflammatory and pro-fibrotic effects of carbon nanotube (CNT). However, the molecular mechanisms of single-walled CNT (SWCNT)-provoked lung injury remain to be elucidated. Here, we established a mice model of SWCNT-induced lung injury by intratracheal instillation and found that C5a-C5a receptor-1 (C5aR1) signaling was significantly activated along with abundant neutrophils recruitment in lungs at early phase post SWCNT administration, which were positively correlated with early lung inflammation and late pulmonary fibrosis. C5a-C5aR1 signaling activation and neutrophils recruitment were subsequently decreased in a time-dependent manner. Furthermore, inhibition of C5a-C5aR1 axis with C5aR1 antagonist PMX205 treatment not only dramatically reduced neutrophils recruitment and inflammatory cytokines secretion at early phase, but also effectively alleviated early lung inflammation and late pulmonary fibrosis induced by SWCNT exposure. In conclusion, our study provides novel insights into the underlying biological mechanism that C5a-C5aR1 axis regulates neutrophils recruitment-mediated lung injury induced by SWCNT, may help to develop therapeutic strategies for SWCNT-provoked lung injury. |
| format | Article |
| id | doaj-art-c2a5e25f09ab42f4804e02d558ab1f86 |
| institution | Kabale University |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-c2a5e25f09ab42f4804e02d558ab1f862025-01-23T05:25:54ZengElsevierEcotoxicology and Environmental Safety0147-65132025-01-01289117627C5a-C5aR1 axis mediates lung inflammation and fibrosis induced by single-walled carbon nanotubes via promoting neutrophils recruitmentJiaojiao Zhu0Xiang Zhang1Lanlan Li2Hongxu Yang3Hang Liu4Danyang Wu5Zikai Liu6Bin Liu7Tong Shen8Department of Occupational Health and Environment Health, School of Public Health, Anhui Medical University, Hefei 230032, ChinaDepartment of Occupational Health and Environment Health, School of Public Health, Anhui Medical University, Hefei 230032, ChinaDepartment of Occupational Health and Environment Health, School of Public Health, Anhui Medical University, Hefei 230032, ChinaDepartment of Occupational Health and Environment Health, School of Public Health, Anhui Medical University, Hefei 230032, ChinaDepartment of Occupational Health and Environment Health, School of Public Health, Anhui Medical University, Hefei 230032, ChinaDepartment of Occupational Health and Environment Health, School of Public Health, Anhui Medical University, Hefei 230032, ChinaDepartment of Occupational Health and Environment Health, School of Public Health, Anhui Medical University, Hefei 230032, ChinaDepartment of Medical Aspects of Specific Environments, School of Basic Medicine, Anhui Medical University, Hefei, ChinaDepartment of Occupational Health and Environment Health, School of Public Health, Anhui Medical University, Hefei 230032, China; Corresponding author.A mounting number of studies have been documenting strong pro-inflammatory and pro-fibrotic effects of carbon nanotube (CNT). However, the molecular mechanisms of single-walled CNT (SWCNT)-provoked lung injury remain to be elucidated. Here, we established a mice model of SWCNT-induced lung injury by intratracheal instillation and found that C5a-C5a receptor-1 (C5aR1) signaling was significantly activated along with abundant neutrophils recruitment in lungs at early phase post SWCNT administration, which were positively correlated with early lung inflammation and late pulmonary fibrosis. C5a-C5aR1 signaling activation and neutrophils recruitment were subsequently decreased in a time-dependent manner. Furthermore, inhibition of C5a-C5aR1 axis with C5aR1 antagonist PMX205 treatment not only dramatically reduced neutrophils recruitment and inflammatory cytokines secretion at early phase, but also effectively alleviated early lung inflammation and late pulmonary fibrosis induced by SWCNT exposure. In conclusion, our study provides novel insights into the underlying biological mechanism that C5a-C5aR1 axis regulates neutrophils recruitment-mediated lung injury induced by SWCNT, may help to develop therapeutic strategies for SWCNT-provoked lung injury.http://www.sciencedirect.com/science/article/pii/S0147651324017032Carbon nanotubeC5a-C5aR1Complement activationLung inflammationPulmonary fibrosis |
| spellingShingle | Jiaojiao Zhu Xiang Zhang Lanlan Li Hongxu Yang Hang Liu Danyang Wu Zikai Liu Bin Liu Tong Shen C5a-C5aR1 axis mediates lung inflammation and fibrosis induced by single-walled carbon nanotubes via promoting neutrophils recruitment Ecotoxicology and Environmental Safety Carbon nanotube C5a-C5aR1 Complement activation Lung inflammation Pulmonary fibrosis |
| title | C5a-C5aR1 axis mediates lung inflammation and fibrosis induced by single-walled carbon nanotubes via promoting neutrophils recruitment |
| title_full | C5a-C5aR1 axis mediates lung inflammation and fibrosis induced by single-walled carbon nanotubes via promoting neutrophils recruitment |
| title_fullStr | C5a-C5aR1 axis mediates lung inflammation and fibrosis induced by single-walled carbon nanotubes via promoting neutrophils recruitment |
| title_full_unstemmed | C5a-C5aR1 axis mediates lung inflammation and fibrosis induced by single-walled carbon nanotubes via promoting neutrophils recruitment |
| title_short | C5a-C5aR1 axis mediates lung inflammation and fibrosis induced by single-walled carbon nanotubes via promoting neutrophils recruitment |
| title_sort | c5a c5ar1 axis mediates lung inflammation and fibrosis induced by single walled carbon nanotubes via promoting neutrophils recruitment |
| topic | Carbon nanotube C5a-C5aR1 Complement activation Lung inflammation Pulmonary fibrosis |
| url | http://www.sciencedirect.com/science/article/pii/S0147651324017032 |
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