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

作　　者：Mai A.ABD-ELMAWLA Heba R.GHAIAD Enas S.GAD Kawkab A.AHMED Maha ABDELMONEM 

机构地区：[1]Department of Biochemistry,Faculty of Pharmacy,Cairo University,Cairo 11562,Egypt [2]Department of Pharmaceutical Sciences,Faculty of Pharmacy,King Faisal University,Al-Ahsa 31982,Saudi Arabia [3]Department of Pharmacology and Toxicology,Faculty of Pharmacy,Sinai University,Ismailia 45511,Egypt [4]Department of Pathology,Faculty of Veterinary Medicine,Cairo University,Cairo 12211,Egypt

出　　处：《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》2023年第8期723-733,共11页浙江大学学报（英文版）B辑（生物医学与生物技术）

基　　金：supported by Open access funding provided by the Science,Technology&Innovation Funding Authority(STDF)in cooperation with the Egyptian Knowledge Bank(EKB).

摘　　要：Ivermectin is a US Food and Drug Administration(FDA)-approved antiparasitic agent with antiviral and anti-inflammatory properties.Although recent studies reported the possible anti-inflammatory activity of ivermectin in respiratory injuries,its potential therapeutic effect on pulmonary fibrosis(PF)has not been investigated.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 manifested by the reduced gene expression of NLRP3 and the apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),with a subsequent decline in the interleukin-1β(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 pulmonary inflammation and fibrosis induced by bleomycin.These beneficial effects were mediated,at least partly,via the downregulation of TGF-β1 and fibronectin,as well as the suppression of NLRP3 inflammasome through modulating the expression of HIF‑1αand NF-κB.

关 键 词：Intra-tracheal instillation Immunohistochemistry Transforming growth factor-β1(TGF-β1) Nuclear factor-κB(NF-κB) Lung fibrosis 

分 类 号：R563[医药卫生—呼吸系统]