Deficiency of interleukin-6 receptor ameliorates PM2.5 exposure-induced pulmonary dysfunction and inflammation but not abnormalities in glucose homeostasis
Background: Ambient fine particulate matter (PM2.5) exposure increases local and systemic interleukin-6 (IL-6). However, the pathogenic role of IL-6 signalling following PM2.5 exposure, particularly in the development of pulmonary dysfunction and abnormal glucose homeostasis, has hardly been investi...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-12-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651322010934 |
| _version_ | 1828128405120352256 |
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| author | Renzhen Peng Wenhui Yang Wenpu Shao Bin Pan Yaning Zhu Yubin Zhang Haidong Kan Yanyi Xu Zhekang Ying |
| author_facet | Renzhen Peng Wenhui Yang Wenpu Shao Bin Pan Yaning Zhu Yubin Zhang Haidong Kan Yanyi Xu Zhekang Ying |
| author_sort | Renzhen Peng |
| collection | DOAJ |
| description | Background: Ambient fine particulate matter (PM2.5) exposure increases local and systemic interleukin-6 (IL-6). However, the pathogenic role of IL-6 signalling following PM2.5 exposure, particularly in the development of pulmonary dysfunction and abnormal glucose homeostasis, has hardly been investigated. Results: In the study, IL-6 receptor (IL-6R)-deficient (IL-6R-/-) and wildtype littermate (IL-6R+/+) mice were exposed to concentrated ambient PM2.5 (CAP) or filtered air (FA), and their pulmonary and metabolic responses to these exposures were analyzed. Our results demonstrated that IL-6R deficiency markedly alleviated PM2.5 exposure-induced increases in lung inflammatory markers including the inflammation score of histological analysis, the number of macrophages in bronchoalveolar lavage fluid (BALF), and mRNA expressions of TNFα, IL-1β and IL-6 and abnormalities in lung function test. However, IL-6R deficiency did not reduce the hepatic insulin resistance nor systemic glucose intolerance and insulin resistance induced by PM2.5 exposure. Conclusion: Our findings support the crucial role of IL-6 signalling in the development of pulmonary inflammation and dysfunction due to PM2.5 exposure but question the putative central role of pulmonary inflammation for the extra-pulmonary dysfunctions following PM2.5 exposure, providing a deep mechanistic insight into the pathogenesis caused by PM2.5 exposure. |
| first_indexed | 2024-04-11T16:04:08Z |
| format | Article |
| id | doaj.art-cafdb987c82c4159b1c27d2081bec9c0 |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-04-11T16:04:08Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-cafdb987c82c4159b1c27d2081bec9c02022-12-22T04:14:52ZengElsevierEcotoxicology and Environmental Safety0147-65132022-12-01247114253Deficiency of interleukin-6 receptor ameliorates PM2.5 exposure-induced pulmonary dysfunction and inflammation but not abnormalities in glucose homeostasisRenzhen Peng0Wenhui Yang1Wenpu Shao2Bin Pan3Yaning Zhu4Yubin Zhang5Haidong Kan6Yanyi Xu7Zhekang Ying8Department of Environmental Health, School of Public Health, Fudan University, Shanghai, ChinaDepartment of Environmental Health, School of Public Health, Fudan University, Shanghai, ChinaDepartment of Environmental Health, School of Public Health, Fudan University, Shanghai, ChinaDepartment of Environmental Health, School of Public Health, Fudan University, Shanghai, ChinaDepartment of Pathology, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huaian, ChinaDepartment of Environmental Health, School of Public Health, Fudan University, Shanghai, ChinaDepartment of Environmental Health, School of Public Health, Fudan University, Shanghai, ChinaDepartment of Environmental Health, School of Public Health, Fudan University, Shanghai, China; Correspondence to: School of Public Health, Fudan University 130 Dong’an Rd, Shanghai 200032, China.Department of Medicine Cardiology Division, University of Maryland School of Medicine, Baltimore, MD, USA; Correspondence to: School of Medicine, University of Maryland 20 Penn St. HSFII S022, Baltimore, MD 21201, USA.Background: Ambient fine particulate matter (PM2.5) exposure increases local and systemic interleukin-6 (IL-6). However, the pathogenic role of IL-6 signalling following PM2.5 exposure, particularly in the development of pulmonary dysfunction and abnormal glucose homeostasis, has hardly been investigated. Results: In the study, IL-6 receptor (IL-6R)-deficient (IL-6R-/-) and wildtype littermate (IL-6R+/+) mice were exposed to concentrated ambient PM2.5 (CAP) or filtered air (FA), and their pulmonary and metabolic responses to these exposures were analyzed. Our results demonstrated that IL-6R deficiency markedly alleviated PM2.5 exposure-induced increases in lung inflammatory markers including the inflammation score of histological analysis, the number of macrophages in bronchoalveolar lavage fluid (BALF), and mRNA expressions of TNFα, IL-1β and IL-6 and abnormalities in lung function test. However, IL-6R deficiency did not reduce the hepatic insulin resistance nor systemic glucose intolerance and insulin resistance induced by PM2.5 exposure. Conclusion: Our findings support the crucial role of IL-6 signalling in the development of pulmonary inflammation and dysfunction due to PM2.5 exposure but question the putative central role of pulmonary inflammation for the extra-pulmonary dysfunctions following PM2.5 exposure, providing a deep mechanistic insight into the pathogenesis caused by PM2.5 exposure.http://www.sciencedirect.com/science/article/pii/S0147651322010934PM2.5IL-6RInflammationPulmonary dysfunctionGlucose homeostasis |
| spellingShingle | Renzhen Peng Wenhui Yang Wenpu Shao Bin Pan Yaning Zhu Yubin Zhang Haidong Kan Yanyi Xu Zhekang Ying Deficiency of interleukin-6 receptor ameliorates PM2.5 exposure-induced pulmonary dysfunction and inflammation but not abnormalities in glucose homeostasis Ecotoxicology and Environmental Safety PM2.5 IL-6R Inflammation Pulmonary dysfunction Glucose homeostasis |
| title | Deficiency of interleukin-6 receptor ameliorates PM2.5 exposure-induced pulmonary dysfunction and inflammation but not abnormalities in glucose homeostasis |
| title_full | Deficiency of interleukin-6 receptor ameliorates PM2.5 exposure-induced pulmonary dysfunction and inflammation but not abnormalities in glucose homeostasis |
| title_fullStr | Deficiency of interleukin-6 receptor ameliorates PM2.5 exposure-induced pulmonary dysfunction and inflammation but not abnormalities in glucose homeostasis |
| title_full_unstemmed | Deficiency of interleukin-6 receptor ameliorates PM2.5 exposure-induced pulmonary dysfunction and inflammation but not abnormalities in glucose homeostasis |
| title_short | Deficiency of interleukin-6 receptor ameliorates PM2.5 exposure-induced pulmonary dysfunction and inflammation but not abnormalities in glucose homeostasis |
| title_sort | deficiency of interleukin 6 receptor ameliorates pm2 5 exposure induced pulmonary dysfunction and inflammation but not abnormalities in glucose homeostasis |
| topic | PM2.5 IL-6R Inflammation Pulmonary dysfunction Glucose homeostasis |
| url | http://www.sciencedirect.com/science/article/pii/S0147651322010934 |
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