Conclusions
Our findings suggest that hydroxychloroquine blocks LMP and can significantly decrease cSiO2-induced toxicity in vitro. HCQ may be a promising treatment for prevention of cSiO2-induced lung damage.
Methods
This study assessed the ability of in vitro treatment with HCQ to block toxicity and lysosomal membrane permeability in cSiO2-exposed mouse bone-marrow derived macrophages. Additionally, C57Bl/6 mice were treated with HCQ by oral gavage before cSiO2 exposure, and the ability of HCQ to prevent lung injury and inflammation was assessed.
Results
In vitro studies demonstrated that HCQ attenuated activation of the NLRP3 inflammasome and blocked LMP. Mice treated with HCQ in vivo showed a modest trend towards decreased cSiO2-induced toxicity. Ex vivo culture of alveolar macrophages collected from cSiO2-treated mice showed significantly less NLRP3 inflammasome activation after in vivo exposure to HCQ. Conclusions: Our findings suggest that hydroxychloroquine blocks LMP and can significantly decrease cSiO2-induced toxicity in vitro. HCQ may be a promising treatment for prevention of cSiO2-induced lung damage.