Role of hypoxia inducible factor 1α in cobalt nanoparticle induced cytotoxicity of human THP-1 macrophages

作     者：Wendy Rachel Francis Zhao Liu Sian E Owens Xiao Wang Huaming Xue Alex Lord Venkateswarlu Kanamarlapudi Zhidao Xia 

作者机构：Centre for NanohealthSwansea University Medical SchoolSwanseaUK Department of Orthopaedic SurgeryOrthopaedic InstituteThe First Affiliated Hospital of Soochow UniversitySuzhouJiangsu ProvinceChina Department of Orthopaedic SurgeryJohns Hopkins School of MedicineBaltimoreMDUSA Department of OrthopaedicsYangpu Hospital affiliated to Tongji University School of MedicineShanghaiChina. 

出 版 物：《Biomaterials Translational》 (生物材料转化电子杂志（英文）)

年 卷 期：2021年第2卷第2期

页      面：143-150页

学科分类：1001[医学-基础医学(可授医学、理学学位)] 100104[医学-病理学与病理生理学] 10[医学] 

主　　题：cobalt nanoparticle cytotoxicity hypoxia inducible factor macrophages TNFα 

摘      要：Cobalt is one of the main components of metal hip prostheses and cobalt nanoparticles(CoNPs)produced from wear cause inflammation,bone lyses and cytotoxicity at high *** ions mimic hypoxia in the presence of normal oxygen levels,and activate hypoxic signalling by stabilising hypoxia inducible transcription factor 1α(HIF1α).This study aimed to assess in vitro the functional role of HIF1αin CoNP induced cellular ***1α,lysosomal pH,tumour necrosis factorαand interleukin 1βexpression were analysed in THP-1 macrophages treated with CoNP(0,10 and 100μg/mL).HIF1αknock out assays were performed using small interfering RNA to assess the role of HIF1αin CoNP-induced *** CoNP concentration increased lysosomal activity and acidity in THP-1 *** doses of CoNP significantly reduced cell viability,stimulated caspase 3 activity and *** HIF1αactivity increased the pro-inflammatory activity of tumour necrosis factorαand interleukin 1β,but had no significant impact on cellular *** suggests that whilst CoNP promotes cytotoxicity and cellular inflammation,the apoptotic mechanism is not dependent on HIF1α.