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

作者机构：Department of BiochemistryFaculty of PharmacyCairo UniversityCairo 11562Egypt Department of Pharmaceutical SciencesFaculty of PharmacyKing Faisal UniversityAl-Ahsa 31982Saudi Arabia Department of Pharmacology and ToxicologyFaculty of PharmacySinai UniversityIsmailia 45511Egypt Department of PathologyFaculty of Veterinary MedicineCairo UniversityCairo 12211Egypt 

出 版 物：《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》 (浙江大学学报（英文版）B辑（生物医学与生物技术）)

年 卷 期：2023年第24卷第8期

页      面：723-733页

核心收录：

学科分类：0710[理学-生物学] 1007[医学-药学(可授医学、理学学位)] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 0905[农学-畜牧学] 0906[农学-兽医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

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

主　　题：Intra-tracheal instillation Immunohistochemistry Transforming growth factor-β1(TGF-β1) Nuclear factor-κB(NF-κB) Lung fibrosis 

摘      要：Ivermectin is a US Food and Drug Administration(FDA)-approved antiparasitic agent with antiviral and anti-inflammatory *** recent studies reported the possible anti-inflammatory activity of ivermectin in respiratory injuries,its potential therapeutic effect on pulmonary fibrosis(PF)has not been *** 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 *** can provide the means to validate the clinical utility of ivermectin as a treatment option for idiopathic *** 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 ***,ivermectin decreased collagen fiber deposition and suppressed transforming growth factor-β1(TGF-β1)and fibronectin protein expression,highlighting its anti-fibrotic *** 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)*** 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 ***,this study revealed that ivermectin could ameliorate pulmonary inflammation and fibrosis induced by *** 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.