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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

  • Inorganic Compounds
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Abstract

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.

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Acknowledgments

This study was financially supported by Grants from National Basic Research Program of China (2011CB503804) and the National Natural Science Foundations of China (81372967 and 81402657). We are indebted to Dr. Paul Borm at the Zuyd University in the Netherlands for providing valuable suggestions and comments.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. 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

    Jiali Guo, Xiuqing Cui, Yi Rong, Ting Zhou, Zhihong Zhang, Yan Shen & Weihong Chen

  2. Medical College, Three Gorges University, Yichang, 443002, Hubei, China

    Jiali Guo

  3. Hubei Center for Disease Prevention and Control, Wuhan, 430079, Hubei, China

    Tingming Shi & Yuewei Liu

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  1. Jiali Guo
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Correspondence to Weihong Chen.

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Jiali Guo and Tingming Shi have contributed equally to this work.

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Guo, J., Shi, T., Cui, X. et al. 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. Arch Toxicol 90, 247–258 (2016). https://doi.org/10.1007/s00204-014-1405-5

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  • DOI: https://doi.org/10.1007/s00204-014-1405-5

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