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

• Published in: Archives of toxicology Vol. 90; no. 2; pp. 247 - 258
• Main Authors: Guo, Jiali, Shi, Tingming, Cui, Xiuqing, Rong, Yi, Zhou, Ting, Zhang, Zhihong, Liu, Yuewei, Shen, Yan, Chen, Weihong
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.02.2016; Springer Nature B.V
• Subjects: Administration, Inhalation; Animals; Antibodies, Monoclonal - pharmacology; Biomedical and Life Sciences; Biomedicine; Cytokines; Cytokines - genetics; Cytokines - metabolism; Environmental Health; Environmental Pollutants - administration & dosage; Environmental Pollutants - toxicity; Epidemiology; Fibrosis - chemically induced; Gene Expression Regulation - drug effects; Heart; Heart - drug effects; Inflammation; Inorganic Compounds; Interleukin-1beta - blood; Interleukin-1beta - immunology; Interleukin-1beta - metabolism; Kidney - drug effects; Kidney - pathology; Kidneys; Male; Mice, Inbred C57BL; Monoclonal antibodies; Myocarditis - chemically induced; Myocarditis - drug therapy; Myocarditis - pathology; Nephritis - chemically induced; Nephritis - drug therapy; Nephritis - pathology; Occupational Medicine/Industrial Medicine; Pharmacology/Toxicology; Silica; Silicon Dioxide - administration & dosage; Silicon Dioxide - toxicity; Heart; Inflammation; IL-1β; Silica; Kidney; Fibrosis
• ISSN: 0340-5761; 1432-0738
• DOI: 10.1007/s00204-014-1405-5

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.