Hepatocyte expression of TRAIL pathway regulators correlates with histopathological and clinical parameters in chronic HCV infection
详细信息 查看全文
- 作者：Sylvia Brost ; Anna Zimmermann ; Ronald Koschny ; Jaromir Sykora ; Wolfgang Stremmel ; Peter Schirmacher ; Henning Walczak ; Tom M. Ganten
- 关键词：cFLIP ; cellular FLICE/caspase-8-inhibitory protein ; cEVR ; complete early viral response ; CMV ; cytomegalovirus ; DR ; death receptor ; EBV ; Epstein&ndash ; Barr virus ; EVR ; early virologic response ; FADD ; FAS-associated via death domain ; HCC ; hepatocellular carcinoma ; IFN ; interferon ; mIgG ; mouse IgG ; NF-魏B ; nuclear factor kappa B ; PEG-IFN ; pegylated interferon alpha ; pEVR ; partial early virologic response ; PLAD ; preligand assembly domain ; RBV ; ribavirin ; RVR ; rapid virologic response ; SVR ; sustained
- 刊名：Pathology - Research and Practice
- 出版年：February, 2014
- 年：2014
- 卷：210
- 期：2
- 页码：83-91
- 全文大小：1924 K
文摘
Background and aims
Treatment with pegylated interferon-alpha (PEG-IFN) and ribavirin is the backbone of standard therapy of HCV by mechanisms that are not completely understood. Besides a direct antiviral effect, different immunomodulatory and apoptotic effects have been discussed. Tumor necrosis factor-related apoptosis inducing-ligand (TRAIL) is a member of the tumor necrosis factor (TNF) family with immunomodulatory as well as pro- and antiapoptotic effects and is putatively involved in control of HCV infection. Thus, we analyzed the expression of the TRAIL/TRAIL-receptor system, caspase-8 and cFLIP and examined their prognostic and predictive value for HCV infection and antiviral therapy, respectively.Methods
We immunohistochemically analyzed liver biopsies of 116 therapy-naive HCV patients before treatment with PEG-IFN伪 and ribavirin in comparison to healthy liver tissue. Expression levels of TRAIL, TRAIL-R1 to TRAIL-R4, caspase-8 and cFLIP were correlated with sustained virologic response (SVR), genotype and staging of chronic hepatitis.
Results
Caspase-8, cFLIP, TRAIL-R2 and TRAIL-R4 were strongly upregulated in HCV patients, whereas TRAIL-R3 was downregulated. SVR correlated with high expression of TRAIL and pro-apoptotic TRAIL-R2 on HCV infected hepatocytes.
Conclusions
Our results suggest a pathophysiological role of TRAIL in both, HCV infection and therapy. Further studies need to elaborate possible TRAIL-related targets for clinical applications.