Obeticholic acid attenuates human immunodeficiency virus/alcohol metabolism-induced pro-fibrotic activation in liver cells
作者机构：Department of EnvironmentalAgriculture and Occupational HealthCollege of Public HealthUniversity of Nebraska Medical CenterOmahaNE 68105United States Research ServiceVeterans Affairs Nebraska-Western Iowa Health Care SystemOmahaNE 68105United States Department of Pharmacology and Experimental NeuroscienceUniversity of Nebraska Medical CenterOmahaNE 68198United States
出 版 物：《World Journal of Hepatology》 (世界肝病学杂志（英文版）（电子版）)
年 卷 期：2020年第12卷第11期
页 面：965-975页
学科分类：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] 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)] 100401[医学-流行病与卫生统计学] 10[医学]
基 金：National Institutes of Health [R01AA027189-01A1]
主 题：Human immunodeficiency virus Liver Obeticholic acid Alcohol Hepatocytes Fibrosis
摘 要：BACKGROUND The morbidity and mortality of human immunodeficiency virus(HIV)-infection is often associated with liver disease,which progresses slowly into severe liver *** are multiple insults which exacerbate HIV-related liver injury,including HIV-associated dysregulation of lipid metabolism and fat turnover,coinfections with hepatotropic viruses and alcohol *** we reported before,exposure of hepatocytes to HIV and alcohol metabolites causes high oxidative stress,impairs proteasomal and lysosomal functions leading to accumulation of HIV in these cells,which end-ups with apoptotic cell death and finally promotes development of liver *** To study whether obeticholic acid(OCA)prevents HIV/ethanol metabolisminduced hepatotoxicity and subsequent activation of hepatic stellate cells(HSC)by HIV+apoptotic hepatocyte *** Huh7.5-CYP(RLW)cells were exposed to HIV and acetaldehyde-generating system(AGS)in the presence or absence of *** the cells,we measured the expression of HIV-related markers:HIVgagRNA-by real-time polymerase chain reaction(PCR),p24-by western blot,HIV DNA-by semi-nested PCR,integrated HIV DNA-by *** and proteasomal activities were measured using fluorometrically-labeled *** hepatocyte apoptosis,cleaved caspase 3 and cleaved PARP were visualized by western blot and cytokeratin 18-by M30 ELISA-in *** bodies were generated from untreated and HIV-treated RLW cells exposed to UV ***-fibrotic activation of HSC was characterized by Col1A1 and transforming growth factor-βmRNAs,while inflammasome activation-by NLRP3,caspase 1,interleukin(IL)-6,IL-1βmRNA *** In RLW cells,OCA treatment attenuated HIV-AGS-induced accumulation of HIVgagRNA,HIV DNA and *** suppressed reactive oxygen species production and restored chymotrypsin-like proteasome activity as well as cathepsin B lysosome *** also decreased HIV-AGS-triggered apoptosis in RLW *** of HI
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