Suppression of NLRP3 inflammasome by ivermectin ameliorates bleomycin-induced pulmonary fibrosis

This study aimed to explore the ability of ivermectin (0.6 mg/kg) to alleviate bleomycin-induced biochemical derangements and histological changes in an experimental PF rat model. This can provide the means to validate the clinical utility of ivermectin as a treatment option for idiopathic PF. The results showed that ivermectin mitigated the bleomycin-evoked pulmonary injury, as manifested by the reduced infiltration of inflammatory cells, as well as decreased the inflammation and fibrosis scores. Intriguingly, ivermectin decreased collagen fiber deposition and suppressed transforming growth factor- β1 (TGF-β1) and fibronectin protein expression, highlighting its anti-fibrotic activity. This study revealed for the first time that ivermectin can suppress the nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome, as manifeste d by the reduced gene expression ofNLRP3 and the apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), with a subsequent decline in the interleukin-1 β (IL-1β) level. In addition, ivermectin inhibited the expression of intracellular nuclear factor-κB (NF-κB) and hypoxia-inducible factor-1α (HIF-1α) proteins along with lowering the oxidative stress and apoptotic markers. Altogether, this study revealed that ivermectin could ameliorate pulmon ary inflammation and fibrosis induced by bleomycin. These beneficial effects were mediated, at least partly,...
Source: Journal of Zhejiang University. Science. B. - Category: Universities & Medical Training Source Type: research