Silica dust exposure induces pulmonary fibrosis through autophagy signaling

Silicosis is a well-acknowledged occupational lung disease caused by inhalation of a large amount of free silica dust during the production period and eventually a considerable negative impact on the patients' quality of life. Autophagy exerts a critical influence on immune and inflammatory responses during the pathogenesis of pulmonary fibrosis. In this study, we sought to determine whether autophagy is involved in silicosis's pathogenesis and how it may affect pulmonary cellular physiology. In the animal experiments, we found persistent activation of autophagy in the development of pulmonary fibrosis, which was also accompanied by tumor necrosis factor and transforming growth factor expression increased. Therefore, the autophagy signaling pathway may regulate the inflammatory response and affect the progression of fibrosis. Further, in vitro experiments, we used LY294002, RAPA, and N-acetylcysteine (NAC) intervened autophagy. Our results showed that PI3K/Akt/mTOR signaling pathway is involved in the autophagy changed mediated by SiO2 exposed, and autophagy might play a protective role in the progression of pulmonary fibrosis. Additionally, NAC's effect is not apparent on SiO2-mediated autophagy through the PI3K/Akt/mTOR signaling pathway, but it can reduce the inflammatory response on NR8383 cells mediated by SiO2-exposed. Nevertheless, it's interesting that NAC can reduce the inflammatory response on NR8383 cells mediated by SiO2-exposed. Taken together, our data demonstrated that SiO2-exposed can induce pulmonary fibrosis along with autophagy both in vivo and in vitro, NAC could alleviate the inflammatory response NR8383 cells by SiO2-exposed through non PI3K/Akt/mTOR signaling pathway, and the specific mechanism of its action needs further studying.

Automated summary

Silicosis is a well-recognized occupational lung disease caused by inhalation of free silica dust, leading to a negative impact on patients' quality of life. Autophagy plays a critical role in the development of pulmonary fibrosis and may affect fibrosis progression through regulating inflammatory response. In vivo and in vitro experiments showed that autophagy signaling pathway, especially PI3K/Akt/mTOR, is involved in the pathogenesis of silicosis-induced pulmonary fibrosis, and NAC could alleviate inflammatory response through a non PI3K/Akt/mTOR pathway.