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

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.

Co-exposure subacute toxicity of silica nanoparticles and lead acetate on cardiovascular system

“…Many studies included six animals/group for toxicological experiments. [11][12][13][14] The concentration of each pollutant was fixed according to the international safety standards specified by WHO. This subacute toxicity model lasted for 30 days and received intra-tracheal instillation for 10 times before being executed.…”

Pro-inflammatory effects of crystalline- and nano-sized non-crystalline silica particles in a 3D alveolar model

“…In particular, pulmonary inflammation may lead to development or exacerbation of cardiovascular disease [26]. In line with this, both occupational exposure and experimental studies in mice suggest that silica-exposure may result in development of cardiovascular outcomes [28][29][30]. As crystalline silica particles are too large to cross the alveolar barrier and enter circulation to any considerable degree, the cause of these effects are most likely due to release of inflammatory mediators.…”

“…Crystalline silica may also cause vascular remodelling in the airways, which may contribute to development of pulmonary hypertension, an irreversible condition associated both with, and complicating, silicosis and COPD [31][32][33]. IL-1α and -β are suggested to be among the key factors involved in development of both pulmonary and cardiovascular effects from silica exposure [30]. IL-1α and IL-1β activate a common IL-1 receptor (IL-1R), and seem via inflammation to be involved in a range of pathological processes [34][35][36].…”

Polyhexamethylene guanidine phosphate induces IL-6 and TNF-α expression through JNK-dependent pathway in human lung epithelial cells

“…1). The cytokines IL-6 and TNF-α are elevated in most, if not all, inflammatory states, and are known to be induced by various stimuli in the lungs (Hao et al, 2000;Rittirsch et al, 2008;Guo et al, 2016;Xu et al, 2016). MAPKs are a large family of proline-directed, serine/ threonine kinases that are activated via dual phosphorylation of certain amino acid residues through multiple signal transduction pathways (Lee et al, 1994;Raingeaud et al, 1995;Son et al, 2011).…”