Another One Fights the Dust: Targeting the NLRP3 Inflammasome for the Treatment of Silicosis
Maggie Lam, Ashley Mansell, Michelle D. Tate
Abstract
Abstract Silicosis is a multifaceted lung disease, characterized by persistent inflammation and structural remodeling. Despite its poor prognosis, there are no treatments currently available for patients with silicosis. Recent preclinical findings in models of lung fibrosis have suggested a major role for the NLRP3 (nucleotide-binding domain and leucine-rich repeat pyrin domain containing 3) inflammasome in silica-driven inflammation and fibrosis. This review outlines the beneficial effects of targeting the NLRP3 inflammasome in in vitro cell experiments and in in vivo animal models, whereby inflammation and fibrosis are abrogated after NLRP3 inflammasome inhibition. Although preclinical evidence is promising, studies that explore NLRP3 inflammasomes in the clinical setting are warranted. In particular, there is still a need to identify biomarkers that may be helpful for the early detection of silicosis and to fully elucidate mechanisms underlying these beneficial effects to further develop or repurpose existing anti-NLRP3 drugs as novel treatments that limit disease progression.