RAB20 deficiency promotes the development of silicosis via NLRP3 inflammasome.

ABSTRACT: Silicosis is a worldwide serious occupational disease that is caused by inhalation of silica crystals. However, little is known about the pathogenesis mechanism of silicosis. We performed single-cell sequencing in bronchoalveolar lavage fluid (BALF) from mine workers with silicosis and their co-workers who did not develop silicosis, and found that the RAB20 deficiency in monocytes/macrophages was strongly linked to the development of silicosis. In the silicosis murine model, RAB20 knockout markedly enhanced the silica crystal-induced pulmonary interstitial fibrosis and respiratory dysfunction. Moreover, this process is strongly accompanied by IL-1β release and NLRP3 activation. In vitro, RAB20 knockout macrophages aggravated the crystalline silica-induced IL-1β release and NLRP3 inf

SUBMITTER: Peng Z 

PROVIDER: S-EPMC9484360 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature