Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0037116 (
silicosis
)
1,822
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Objectives:
Inhalation of crystalline silica (cSiO
2
) remains a significant occupational hazard and may lead to the development of
silicosis
. When cSiO
2
particles are phagocytized by alveolar macrophages, they cause disruption of the lysosomal membrane which results in cell death. There are currently no pharmaceutical treatments directed at this mechanism of disease; however, many existing pharmaceuticals, such as hydroxychloroquine (HCQ), become sequestered in the lysosome through an ion-trapping mechanism. The objective of this research was to determine whether HCQ can prevent cSiO
2
-induced toxicity by blocking
LMP
in alveolar macrophages.
Materials and methods:
This study assessed the ability of
in vitro
treatment with HCQ to block toxicity and lysosomal membrane permeability in cSiO
2
-exposed mouse bone-marrow derived macrophages. Additionally, C57Bl/6 mice were treated with HCQ by oral gavage before cSiO
2
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 cSiO
2
-induced toxicity.
Ex vivo
culture of alveolar macrophages collected from cSiO
2
-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 cSiO
2
-induced toxicity
in vitro
. HCQ may be a promising treatment for prevention of cSiO
2
-induced lung damage.
...
PMID:Prevention of crystalline silica-induced inflammation by the anti-malarial hydroxychloroquine. 3155 48
