Effects of silica exposure on the cardiac and renal inflammatory and fibrotic response and the antagonistic role of interleukin-1 beta in C57BL/6 mice.
Current epidemiological studies suggest that crystalline silica exposure is associated with an increased risk of cardiovascular and renal disease; however, the potential pathological damage of the heart and kidney and its underlying mechanisms have not been completely elucidated. This study tried to investigate the silica-induced inflammatory and fibrotic changes in the heart and kidney and evaluate the role of interleukin (IL)-1 beta (β) in silica-induced cardiac and renal damage. In this study, a silica-exposed model was generated by intratracheally instilling silica dust in mice. The anti-IL-1β monoclonal antibody (mAb) was used to neutralise IL-1β in the pulmonary alveolus and serum. The real-time PCR studies showed that (1) inhalational silica induced inflammatory responses in the heart and kidney by elevated mRNA levels of TNF-α, IL-6 and MCP-1; (2) early fibrotic responses in the heart were observed as elevated mRNA levels of collagen I and fibronectin. What is more, fibrosis of the kidney was demonstrated by pathological results and significantly increased mRNA levels of TGF-β, collagen I, collagen III and fibronectin. Further studies showed that usage of anti-IL-1β mAb decreased the inflammatory response of the heart and kidney induced by inhalational silica and also attenuated fibrosis in the mouse kidney. In conclusion, this study found that inhaled silica induced inflammatory and early fibrotic responses in the mouse heart and inflammatory response and fibrosis in the mouse kidney. Neutralisation of IL-1β attenuated the silica-induced inflammatory response of the heart and kidney and decreased fibrosis in the mouse kidney.
Department of Occupational and Environmental Health and Key Laboratory of Environment and Health, Ministry of Education and Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.|Medical College, Three Gorges University, Yichang, 443002, Hubei, China.
Jiali
J
Guo
Hubei Center for Disease Prevention and Control, Wuhan, 430079, Hubei, China.
Tingming
T
Shi
Department of Occupational and Environmental Health and Key Laboratory of Environment and Health, Ministry of Education and Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.
Xiuqing
X
Cui
Department of Occupational and Environmental Health and Key Laboratory of Environment and Health, Ministry of Education and Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.
Yi
Y
Rong
Department of Occupational and Environmental Health and Key Laboratory of Environment and Health, Ministry of Education and Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.
Ting
T
Zhou
Department of Occupational and Environmental Health and Key Laboratory of Environment and Health, Ministry of Education and Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.
Zhihong
Z
Zhang
Hubei Center for Disease Prevention and Control, Wuhan, 430079, Hubei, China.
Yuewei
Y
Liu
Department of Occupational and Environmental Health and Key Laboratory of Environment and Health, Ministry of Education and Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.
Yan
Y
Shen
Department of Occupational and Environmental Health and Key Laboratory of Environment and Health, Ministry of Education and Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China. wchen@mails.tjmu.edu.cn.
Weihong
W
Chen
D000280:Administration, Inhalation; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000633:toxicity; D005355:Fibrosis / Q000139:chemically induced; D005786:Gene Expression Regulation / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D053583:Interleukin-1beta / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D009205:Myocarditis / Q000139:chemically induced* / Q000188:drug therapy / Q000473:pathology; D009393:Nephritis / Q000139:chemically induced* / Q000188:drug therapy / Q000473:pathology; D012822:Silicon Dioxide / Q000008:administration & dosage / Q000633:toxicity*
D000911:Antibodies, Monoclonal; D016207:Cytokines; D004785:Environmental Pollutants; D053583:Interleukin-1beta; D012822:Silicon Dioxide
Fibrosis; Heart; IL-1β; Inflammation; Kidney; Silica