Pulmonary inflammatory and fibrogenic response induced by graphitized multi-walled carbon nanotube involved in cGAS-STING signaling pathway.

Abstract Graphitized multi-walled carbon nanotubes (GMWCNTs) are a new type of nanomaterial. Recently, their production and application in biological medicine have grown rapidly. However, GMWCNTs may cause adverse health effects, including the common occupational disease of pulmonary fibrosis. Pulmonary fibrosis is a serious progressive disease that often leads to lung failure, high mortality, and disability, and there is no effective therapy currently available. Therefore, identifying new biomarkers of the disease is important to better understand the disease mechanisms and explore new therapeutic strategies. In this study, 40 μg of GMWCNTs was used to treat mice in vivo by pharyngeal aspiration, and different genes were screened by transcriptome sequencing. Activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon gene (STING) signal pathway had an important effect on the development of pulmonary inflammation and fibrosis. GMWCNTs were then administered to the mice with a STING inhibitor (C-176). Inhibition of STING effectively decreased pulmonary inflammation and fibrosis in mice induced by GMWCNTs. Collectively, activation of the cGAS-STING signaling pathway is involved in GMWCNT-induced pulmonary inflammation and fibrosis in mice.