Cholesterol-dependent molecular mechanisms contribute to cationic amphiphilic drugs' prevention of silica-induced inflammation.

ABSTRACT: Silicosis is considered an irreversible chronic inflammatory disease caused by the inhalation of crystalline silica (cSiO₂). The cycle of inflammation that drives silicosis and other particle-caused respiratory diseases is mediated by NLRP3 inflammasome activity in macrophages resulting in the release of IL-1β. Lysosomal membrane permeability (LMP) initiated by inhaled particles is the key regulatory step in leading to NLRP3 activity. In addition to its role in LMP, the lysosome is crucial to cellular cholesterol trafficking. Lysosomal cholesterol has been demonstrated to regulate LMP while cationic amphiphilic drugs (CADs) reduce cholesterol trafficking from lysosomes and promote endolysosomal cholesterol accumulation as seen in Niemann Pick disease. Using a bone marrow derived

SUBMITTER: Kendall RL 

PROVIDER: S-EPMC10330738 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature