Affiliation:
1. Occupational Disease and Toxicology Department, Beijing Chao-Yang Hospital, Capital Medical University , Beijing 100020, China
2. Department of Pathology, Beijing Chao-Yang Hospital, Capital Medical University , Beijing 100020, China
Abstract
Abstract
Background
Inhalation of silica crystals in occupational settings is a main cause of silicosis, a chronic irreversible pulmonary disorder. Our prior studies demonstrated the activation of inflammasome sensors AIM2 and NLRP3, effector protein caspase-1, and significant increase in IL-1β in silica exposed rats, suggesting that the canonical inflammasome activation may be associated with silica-induced tissue damage and inflammation.
Aims and Methods
In our current study using the same animal model system, we further evaluated the components of non-canonical inflammasome, including NEK7, caspase-11, and GSDMD following silica exposure.
Results
We demonstrated sustained NEK7 elevation in the rat lung epithelial cells and macrophages following 1- and 3-day exposure. Enhanced NEK7 expression was also detected in lung homogenate by western blot. Similarly, caspase-11 expression was induced by silica exposure in lung sections and homogenate. Elevated GSDMD was observed both in lung sections by immunohistochemical staining and in lung tissue homogenate by western blot.
Conclusion
In summary, our current study demonstrated increase in NEK7, caspase-11, and GSDMD in silica exposed rats, indicating activation of non-canonical inflammasome complex, thereby providing a broad inflammasome activation pathway caused by silica exposure.
Publisher
Oxford University Press (OUP)
Subject
Health, Toxicology and Mutagenesis,Toxicology