TLR4 signaling and the inhibition of liver hepcidin expression by alcohol

作     者：Emily Zmijewski Sizhao Lu Duygu Dee Harrison-Findik 

作者机构：Department of Internal MedicineUniversity of Nebraska Medical CenterOmahaNE 68198-5820United States 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2014年第20卷第34期

页      面：12161-12170页

核心收录：

学科分类：1002[医学-临床医学] 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 NIH grant No.R01AA017738(to Harrison Findik DD) University of Nebraska Medical Center Undergraduate Scholarship(to Lu S) 

主　　题：Iron Small heterodimer partner protein Nuclear fac 

摘      要：AIM:To understand the role of toll-like receptor 4(TLR4)signaling in the regulation of iron-regulatory hormone,hepcidin by chronic alcohol ***:For chronic alcohol intake studies,TLR4mutant mice on C3H/HeJ background and wildtype counterpart on C3H/HeOuJ background were pair-fed with regular(control)and ethanol-containing Lieber De Carli liquids *** expression was determined by real-time quantitative ***-protein interactions and protein expression were determined by co-immunoprecipitation and western *** occupancy of hepcidin gene promoter was determined by chromatin immunoprecipitation ***:Chronic alcohol intake suppressed hepcidin mRNA expression in the livers of wildtype,but not TLR4 mutant,*** phosphorylation and nuclear translocation of nuclear factor(NF)-κB p65 subunit protein was observed in alcohol-fed wildtype,but not in alcohol-fed TLR4 mutant,***,alcohol induced the binding of NF-κB p50 subunit protein to hepcidin gene promoter in wildtype,but not in TLR4mutant,*** contrast,the phosphorylation of Stat3in the liver was stronger in alcohol-treated TLR4 mutant mice compared to alcohol-treated wildtype *** occupancy of hepcidin gene promoter by Stat3was observed in alcohol-fed mutant,but not in wildtype,*** interaction between NF-κB p65 subunit protein and small heterodimer partner protein(SHP)was observed in the livers of both wildtype and TLR4mutant mice fed with the control diet,as shown by coimmunoprecipitation *** intake elevated cytosolic SHP expression but attenuated its interaction with NF-κB in the liver,which was more prominent in the livers of wildtype compared to TLR4 mutant ***:Activation of TLR4 signaling and NF-кB are involved in the suppression of hepcidin gene transcription by alcohol in the presence of inflammation in the liver.