Abstract:
BACKGROUND & AIM:Virus-induced fulminant hepatitis is a major cause of acute liver failure. During acute viral hepatitis the impact of type I interferon (IFN-I) on myeloid cells, including liver-resident Kupffer cells (KC), is only partially understood. Herein, we dissected the impact of locally induced IFN-I responses on myeloid cell function and hepatocytes during acute liver inflammation. METHODS:Two different DNA-encoded viruses, vaccinia virus (VACV) and murine cytomegalovirus (MCMV), were studied. In vivo imaging was applied to visualize local IFN-β induction and IFN-I receptor (IFNAR) triggering in VACV-infected reporter mice. Furthermore, mice with a cell type-selective IFNAR ablation were analyzed to dissect the role of IFNAR signaling in myeloid cells and hepatocytes. Experiments with Cx3cr1+/gfp mice revealed the origin of reconstituted KC. Finally, mixed bone marrow chimeric mice were studied to specifically analyze the effect of IFNAR triggering on liver infiltrating monocytes. RESULTS:VACV infection induced local IFN-β responses, which lead to IFNAR signaling primarily within the liver. IFNAR triggering was needed to control the infection and prevent fulminant hepatitis. The severity of liver inflammation was independent of IFNAR triggering of hepatocytes, whereas IFNAR triggering of myeloid cells protected from excessive inflammation. Upon VACV or MCMV infection KC disappeared, whereas infiltrating monocytes differentiated to KC afterwards. During IFNAR triggering such replenished monocyte-derived KC comprised more IFNAR-deficient than -competent cells in mixed bone marrow chimeric mice, whereas after the decline of IFNAR triggering both subsets showed an even distribution. CONCLUSION:Upon VACV infection IFNAR triggering of myeloid cells, but not of hepatocytes, critically modulates acute viral hepatitis. During infection with DNA-encoded viruses IFNAR triggering of liver-infiltrating blood monocytes delays the development of monocyte-derived KC, pointing towards new therapeutic strategies for acute viral hepatitis. LAY SUMMARY:Viral infection can cause fulminant hepatitis, which in turn is a major cause of acute liver failure. Herein, we aimed to study the role of type 1 interferon responses in acute viral hepatitis. We identified that during infection with DNA-encoded viruses, type 1 interferon receptor triggering of blood monocytes delays the development of monocyte-derived Kupffer cells. This points to new therapeutic strategies for acute viral hepatitis.
journal_name
J Hepatoljournal_title
Journal of hepatologyauthors
Borst K,Frenz T,Spanier J,Tegtmeyer PK,Chhatbar C,Skerra J,Ghita L,Namineni S,Lienenklaus S,Köster M,Heikenwaelder M,Sutter G,Kalinke Udoi
10.1016/j.jhep.2017.11.029subject
Has Abstractpub_date
2018-04-01 00:00:00pages
682-690issue
4eissn
0168-8278issn
1600-0641pii
S0168-8278(17)32473-Xjournal_volume
68pub_type
杂志文章abstract:BACKGROUND/AIMS:We have developed a gene therapy strategy based on the observation that insulin-like growth factor I (IGF-I) is necessary for the acquisition and maintenance of the transformed phenotype in hepatocarcinoma. This strategy consists in transfecting the rat hepatoma cell line with an episomal vector express...
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abstract::The mechanism responsible for liver cell necrosis in patients with hepatitis A is not known. Since the type of hepatic lesions and the clinical presentation of acute hepatitis B are similar and are probably related to the cell-mediated immune response to a viral antigen located in the liver cell, it is possible that a...
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doi:10.1016/j.jhep.2016.11.003
更新日期:2017-04-01 00:00:00
abstract::Over the last three decades acute liver failure (ALF) has been transformed from a rare and poorly understood condition with a near universally fatal outcome, to one with a well characterized phenotype and disease course. Complex critical care protocols are now applied and emergency liver transplantation (ELT) is an es...
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更新日期:2018-07-01 00:00:00
abstract:BACKGROUND/AIMS:The use of cell lines in bioartificial liver support systems (BALSS) to treat fulminant hepatic failure (FHF) is hindered by their reduced metabolic functions, which could be further decreased by the patient's serum/plasma. Hence, the aim of this study was to (i) test the effect of the FHF serum on C3A ...
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doi:10.1016/j.jhep.2004.06.012
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journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(02)00269-6
更新日期:2002-11-01 00:00:00
abstract:BACKGROUND & AIMS:Therapeutic options for patients failing hepatitis C retreatment are limited. EPIC(3) included a prospective trial assessing long-term peginterferon alfa-2b (PegIFNα-2b) maintenance therapy in patients with METAVIR fibrosis scores (MFS) of F2 or F3 who previously failed hepatitis C retreatment. METHO...
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pub_type: 杂志文章,多中心研究,随机对照试验
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更新日期:2013-03-01 00:00:00
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journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2005.02.045
更新日期:2005-10-01 00:00:00
abstract:BACKGROUND:The association between polyarteritis nodosa and viral hepatitis B infection is well established and still remains a therapeutic challenge. Famciclovir--a new nucleoside analog--has a broad spectrum of antiviral activity against herpes viruses and the human hepatitis B virus. CASE REPORT:A 56-year-old man w...
journal_title:Journal of hepatology
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doi:10.1016/s0168-8278(97)80263-2
更新日期:1997-04-01 00:00:00
abstract::Hepatitis C virus (HCV) infects mononuclear cells and may be responsible, as are other viruses, for immunologic disorders. The immunologic abnormalities observed in HCV infections are usually non-specific (i.e. cryoglobulinemia, immune complex deposits, autoantibodies). The association with cryoglobulinemia is clear a...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/s0168-8278(99)80404-8
更新日期:1999-01-01 00:00:00
abstract:BACKGROUND/AIMS:Alamifovir is a purine nucleotide analogue prodrug that shows potent activity against wild type and lamivudine resistant hepatitis B virus in preclinical studies. The aim of this study was to assess the safety and potential antiviral effects of alamifovir in humans. METHODS:A randomised, placebo contro...
journal_title:Journal of hepatology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/j.jhep.2004.07.028
更新日期:2004-11-01 00:00:00
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journal_title:Journal of hepatology
pub_type: 杂志文章
doi:
更新日期:1995-01-01 00:00:00
abstract:BACKGROUND/AIMS:Apoptosis of bile duct cells occurs in hepatic allografts and is correlated with acute rejection. bcl-2 protein counteracts apoptosis and prolongs cell survival. We therefore tested the expression of bcl-2 protein in bile ducts of liver grafts in comparison with those of liver cirrhosis. METHODS:115 bi...
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pub_type: 杂志文章
doi:10.1016/s0168-8278(97)80418-7
更新日期:1997-03-01 00:00:00
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journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(03)00385-4
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journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2013.05.026
更新日期:2013-10-01 00:00:00
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journal_title:Journal of hepatology
pub_type: 杂志文章,多中心研究
doi:10.1016/j.jhep.2016.07.010
更新日期:2017-01-01 00:00:00
abstract:BACKGROUND/AIMS:Liver carbohydrate metabolism and blood flow are regulated by hepatic nerves and hormones such as glucagon, insulin or catecholamines. Acute and chronic application of alcohol are known to depress the function of central and peripheral nerves. The extent of inhibition of the autonomic nervous system is ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(97)80025-6
更新日期:1997-01-01 00:00:00
abstract:BACKGROUND & AIMS:In non-alcoholic fatty liver disease (NAFLD), hepatocytes can undergo necroptosis: a regulated form of necrotic cell death mediated by the receptor-interacting protein kinase (RIPK) 1. Herein, we assessed the potential for RIPK1 and its downstream effector mixed lineage kinase domain-like protein (MLK...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2019.11.008
更新日期:2020-04-01 00:00:00
abstract::The presence of hepatitis B virus DNA (HBV-DNA) in the peripheral blood mononuclear cells (PBMC) of 29 anti-HIV symptomless carriers (eleven HBeAg positive, eleven anti-HBe positive and seven HBsAg negative) and of 40 anti-human immunodeficiency virus (HIV)-negative patients (15 HBeAg positive, 15 anti-HBe positive an...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(90)90050-2
更新日期:1990-03-01 00:00:00
abstract:BACKGROUND & AIMS:Liver failure is associated with progressive cytotoxic brain oedema (astrocyte swelling), which underlies hepatic encephalopathy (HE). Ammonia and superimposed inflammation are key synergistic factors in HE, but the mechanism(s) involved remain unknown. We aimed to determine whether aquaporin-4 (AQP4)...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2010.02.020
更新日期:2010-07-01 00:00:00
abstract::Since interferons are reported to inhibit collagen synthesis in vivo and in vitro, they are possible anti-fibrogenic drugs. However, little is known about the effect of interferons on connective tissue metabolism in liver disease. To investigate the effect, serum concentrations of the aminoterminal domain of procollag...
journal_title:Journal of hepatology
pub_type: 临床试验,杂志文章
doi:10.1016/s0168-8278(05)80173-4
更新日期:1993-08-01 00:00:00
abstract:BACKGROUND & AIMS:The insignificance of pure microsteatosis (MiS) was reported in living donor liver transplantation (LDLT). However, since steatosis is mostly found in a mixed form of microsteatosis (MiS) and macrosteatosis (MaS), we aimed to determine the importance of MiS mixed with MaS in LDLT. METHODS:Donor match...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2014.10.027
更新日期:2015-03-01 00:00:00
abstract:BACKGROUND/AIMS:Hepatic stellate cells (HSCs) are known to play a role in hepatic regeneration. We investigated hepatocyte/HSC interaction and HSC activation at various times after 70% partial hepatectomy (PHx) in the rat. METHODS:The hepatic microcirculation was studied using intravital fluorescence microscopy (IVFM)...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2004.02.005
更新日期:2004-06-01 00:00:00
abstract:BACKGROUND/AIMS:Whether GB virus C and hepatitis G virus participate in fulminant hepatic failure is controversial. We studied the prevalence of the viral RNA in 48 patients. There were possible routes of infection, including blood transfusion, in 22 patients (group 1), and no risk factors in the other 26 (group 2). M...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(97)80138-9
更新日期:1997-12-01 00:00:00