Abstract:
BACKGROUND & AIM:Alcohol consumption increases intestinal permeability and causes damage to hepatocytes, leading to the release of pathogen- and damage-associated molecular pattern molecules (PAMPs and DAMPs), stimulating hepatic macrophages and activating NF-κB. The resultant inflammation exacerbates alcoholic liver disease (ALD). However, much less is known about the mechanisms attenuating inflammation and preventing disease progression in most heavy drinkers. Interleukin (IL)-33 is a DAMP (alarmin) released from dead cells that acts through its receptor, IL-1 receptor like 1 (ST2). ST2 signaling has been reported to either stimulate or inhibit NF-κB activation. The role of IL-33/ST2 in ALD has not been studied. METHODS:Serum levels of IL-33 and its decoy receptor, soluble ST2 (sST2) were measured in ALD patients. Alcohol-induced liver injury, inflammation and hepatic macrophage activation were compared between wild-type, IL-33-/- and ST2-/- mice in several models. RESULTS:Elevation of serum IL-33 and sST2 were only observed in patients with severe decompensated ALD. Consistently, in mice with mild ALD without significant cell death and IL-33 release, IL-33 deletion did not affect alcohol-induced liver damage. However, ST2-deletion exacerbated ALD, through enhancing NF-κB activation in liver macrophages. In contrast, when extracellular IL-33 was markedly elevated, liver injury and inflammation were attenuated in both IL-33-/- and ST2-/- mice compared to wild-type mice. CONCLUSION:Our data revealed a dichotomous role of IL-33/ST2 signaling during ALD development. At early and mild stages, ST2 restrains the inflammatory activation of hepatic macrophages, through inhibiting NF-κB, and plays a protective function in an IL-33-independent fashion. During severe liver injury, significant cell death and marked IL-33 release occur, which triggers IL-33/ST2 signaling and exacerbates tissue damage. LAY SUMMARY:In mild ALD, ST2 negatively regulates the inflammatory activation of hepatic macrophages, thereby protecting against alcohol-induced liver damage, whereas in the case of severe liver injury, the release of extracellular IL-33 may exacerbate tissue inflammation by triggering the canonical IL-33/ST2L signaling in hepatic macrophages.
journal_name
J Hepatoljournal_title
Journal of hepatologyauthors
Wang M,Shen G,Xu L,Liu X,Brown JM,Feng D,Ross RA,Gao B,Liangpunsakul S,Ju Cdoi
10.1016/j.jhep.2017.08.023subject
Has Abstractpub_date
2017-09-21 00:00:00eissn
0168-8278issn
1600-0641pii
S0168-8278(17)32263-8pub_type
杂志文章abstract:BACKGROUND/AIMS:The world-wide distribution of hepatitis B virus (HBV) genotypes follows a geographic pattern under the influence of ethnic background. METHODS:Forty eight core genes from four pacific islands were compared with the following findings. RESULTS:First, island-specific variant substitutions were found fo...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2004.03.025
更新日期:2004-07-01 00:00:00
abstract::Interferon-alpha therapy has a beneficial effect in 30-40% of selected patients with chronic hepatitis B who respond by clearing hepatitis B e antigen (HBeAg) and hepatitis B viral (HBV) DNA from serum. This is usually associated with normalization of serum aminotransferase activities. On long-term follow-up of treate...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:
更新日期:1995-01-01 00:00:00
abstract::Current medical practice artificially dichotomises a diagnosis of fatty liver disease into one of two common forms: alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD). Together, these account for the majority of chronic liver diseases worldwide. In recent years, there has been a dramatic incre...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2017.11.006
更新日期:2018-02-01 00:00:00
abstract::Interleukin 6 (IL-6) is a pleiotropic four-helix-bundle cytokine that exerts multiple functions in the body. In the liver, IL-6 is an important inducer of the acute phase response and infection defense. IL-6 is furthermore crucial for hepatocyte homeostasis and is a potent hepatocyte mitogen. It is not only implicated...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2016.02.004
更新日期:2016-06-01 00:00:00
abstract::To establish the effects of a meal on portal venous flow and the prognostic value of this parameter, 46 patients with chronic liver disease and 28 healthy subjects were examined with duplex Doppler before and after a meal. The measurements were completed in 40 patients and 21 healthy subjects. Postprandial portal veno...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(05)80603-8
更新日期:1994-12-01 00:00:00
abstract:BACKGROUND/AIMS:No information is yet available about the influence of alcohol abuse on the translocation of larger molecules (Mr>1200) through the intestinal mucosa in man. The present study aimed to determine the intestinal permeability to macromolecules in patients with chronic alcohol abuse and mild to more advance...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(00)80242-1
更新日期:2000-05-01 00:00:00
abstract::Eighty-eight dialysis patients were vaccinated with recombinant hepatitis B vaccine prepared in yeast. Fourty-nine patients were immunized 3 times (months 0, 1, 6) intragluteally with 40 micrograms hepatitis B surface antigen (HBsAg) per dose. Only 32 of them (65.3%) showed anti-HBs concentrations above 10 IU/l with a...
journal_title:Journal of hepatology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/s0168-8278(86)80025-3
更新日期:1986-01-01 00:00:00
abstract:BACKGROUND & AIMS:Lysosomal acid lipase deficiency is an autosomal recessive enzyme deficiency resulting in lysosomal accumulation of cholesteryl esters and triglycerides. LAL-CL04, an ongoing extension study, investigates the long-term effects of sebelipase alfa, a recombinant human lysosomal acid lipase. METHODS:Seb...
journal_title:Journal of hepatology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1016/j.jhep.2014.06.022
更新日期:2014-11-01 00:00:00
abstract:BACKGROUND/AIMS:To review our experience of thrombolytic therapy in patients with acute Budd Chiari syndrome (BCS). METHODS:Records of 10 patients with BCS, treated by thrombolysis over a 12-year period were retrospectively analysed for demographics, clinical presentation/duration, primary disease, thrombolytic regime...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2003.09.028
更新日期:2004-01-01 00:00:00
abstract::Because of the tremendous success of clinical transplantation of the liver and other organs in the last three decades, the demand for organs for transplantation has risen sharply and there is now a substantial shortage. The utilization of organs from other species, xenotransplantation, is increasingly viewed as a pote...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/s0168-8278(96)80082-1
更新日期:1996-08-01 00:00:00
abstract::In a follow-up study of 3 years' duration, serum inhibitory factors (SIF) were analysed in 23 patients with a protracted course of viral hepatitis B (PVH) and 12 patients with chronic persistent hepatitis (CPH). Four patients showed a progressive course, developing chronic active hepatitis, and one died of liver failu...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(87)80083-1
更新日期:1987-04-01 00:00:00
abstract:BACKGROUND & AIMS:We applied advanced magnetic resonance imaging and Voxed based Morphometry analysis to assess brain tissue density in patients with cirrhosis. METHODS:Forty eight patients with cirrhosis without overt hepatic encephalopathy (17 Child A, 13 Child B, and 18 Child C) and 51 healthy subjects were matched...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2010.12.008
更新日期:2011-09-01 00:00:00
abstract:BACKGROUND & AIMS:Liver stiffness (LS) as measured by transient elastography [Fibroscan] offers a novel non-invasive approach to assess liver cirrhosis. Since Fibroscan seems to be unreliable in patients with congestive heart failure, it remains to be determined whether hemodynamic changes affect LS irrespective of fib...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2009.11.018
更新日期:2010-02-01 00:00:00
abstract::We previously reported that high-dose ursodeoxycholate (UDC) infusion in rats resulted in extensive glucuronidation of UDC, and speculated that the glucuronidation causes bicarbonate-rich hypercholeresis induced by UDC (Takikawa, H., Sano, N., Narita, T. and Yamanaka, M. Hepatology 1990; 11: 743-749). To test this hyp...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(92)90015-h
更新日期:1992-05-01 00:00:00
abstract:BACKGROUND & AIMS:Living donor liver transplantation (LDLT) provides a timely alternative to deceased donor liver transplantation (DDLT) for patients with hepatitis C virus-related (HCV-related) diseases in the circumstances of severe organ dearth. However, the patient and graft outcomes, and recurrence of HCV after LD...
journal_title:Journal of hepatology
pub_type: 杂志文章,meta分析,评审
doi:10.1016/j.jhep.2012.07.015
更新日期:2012-12-01 00:00:00
abstract:BACKGROUND & AIMS:Resveratrol, a polyphenol found in a variety of fruits, exerts a wide range of beneficial effects on the endothelium, regulates multiple vasoactive substances and decreases oxidative stress, factors involved in the pathophysiology of portal hypertension. Our study aimed at evaluating the effects of re...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2012.12.012
更新日期:2013-05-01 00:00:00
abstract:BACKGROUND & AIMS:Hallmarks of non-alcoholic fatty liver disease (NAFLD) are increased triglyceride accumulation within hepatocytes. The prevalence of NAFLD increases steadily with increasing thyrotropin (TSH) levels. However, the underlying mechanisms are largely unknown. Here, we focused on exploring the effect and m...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2014.06.037
更新日期:2014-12-01 00:00:00
abstract:BACKGROUND/AIMS:Despite anti-HBs immunoglobulin therapy, hepatitis B virus (HBV) infection recurs in a high proportion of patients transplanted for HBsAg positive and serum HBV DNA negative chronic liver disease. The contribution of HBV genetic variability to disease recurrence has not been yet thoroughly addressed. We...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(97)80035-9
更新日期:1997-02-01 00:00:00
abstract:AIM:In order to study the short-term effect of moderate and severe reduction of liver function by acetaminophen poisoning of different severity on gene expression for liver-specific functions, rats were given 3.75 and 7.5 g per kg body weight acetaminophen intragastrically. The lower dose is associated with low mortali...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(96)80072-9
更新日期:1996-08-01 00:00:00
abstract:BACKGROUND/AIMS:The aim was to study the reproducibility of magnetic resonance velocity mapping, when measuring portal vein and superior mesenteric artery blood flow, under fasting and post-prandial conditions. Magnetic resonance flow measurements for the portal vein were compared with echo-Doppler measurements in the ...
journal_title:Journal of hepatology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/s0168-8278(97)80045-1
更新日期:1997-02-01 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
pub_type: 杂志文章
doi:10.1016/s0168-8278(97)80263-2
更新日期:1997-04-01 00:00:00
abstract:BACKGROUND & AIMS:Robust data on hepatocellular carcinoma (HCC) incidence among HIV/hepatitis B virus (HBV)-coinfected individuals on antiretroviral therapy (ART) are needed to inform HCC screening strategies. We aimed to evaluate the incidence and risk factors of HCC among HIV/HBV-coinfected individuals on tenofovir d...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2019.03.032
更新日期:2019-08-01 00:00:00
abstract::Reactivation of Hedgehog (Hh), a morphogenic signaling pathway that controls progenitor cell fate and tissue construction during embryogenesis occurs during many types of liver injury in adult. The net effects of activating the Hedgehog pathway include expansion of liver progenitor populations to promote liver regener...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2010.10.003
更新日期:2011-02-01 00:00:00
abstract:BACKGROUND/AIMS:We assessed mitochondrial morphology by electron microscopy and the prevalence of a mitochondrial gene deletion in patients with non-alcoholic steatohepatitis (NASH), alcohol-related liver disease and non-fatty liver diseases. Respiratory chain function using a cytoplasmic hybrid (cybrid) assay was furt...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(99)80033-6
更新日期:1999-09-01 00:00:00
abstract:BACKGROUND & AIMS:We previously showed that Reptin is overexpressed in hepatocellular carcinoma (HCC), and that in vitro depletion of Reptin with siRNAs led to HCC cell growth arrest and apoptosis. Here, we asked whether in vivo targeting of Reptin in established tumours had a therapeutic effect. METHODS:We used lenti...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2009.12.029
更新日期:2010-05-01 00:00:00
abstract:BACKGROUND/AIMS:Hepatic stellate cells (HSCs) are perisinusoidal pericytes which have receptors for vasoactive factors, such as endothelin-1, which can regulate cell contractility in an autocrine manner. It is unknown whether human HSCs have receptors for and are able to synthesize the vasodilator peptide adrenomedulli...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(00)00016-7
更新日期:2001-02-01 00:00:00
abstract:BACKGROUND & AIMS:Genetic background may affect liver damage in patients with non-alcoholic fatty liver disease (NAFLD). The main outcomes of the study were to assess whether IL28B rs12979860 and rs8099917 polymorphisms, together with PNPLA3 rs738409 C>G polymorphism, are associated with lobular inflammation and fibros...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2012.01.007
更新日期:2012-06-01 00:00:00
abstract:BACKGROUND/AIMS:ATP stimulation of purinergic P2 receptors (P2YR and P2XR) regulates several hepatic functions. Here we report the involvement of ATP-mediated signals in enhancing hepatocyte tolerance to lethal stress. METHODS:The protection given by purinergic agonists was investigated in rat hepatocytes exposed to h...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2006.02.017
更新日期:2006-08-01 00:00:00
abstract::Rats were malnourished for 12 months with a highly inadequate fat-rich, calorie-sufficient but otherwise poly-deficient liquid diet composed of mashed potatoes with mayonnaise, comparable with the nutritional intake of many chronic alcoholics. When alcohol was incorporated into this diet, administered as whisky in dri...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(05)80319-8
更新日期:1994-09-01 00:00:00
abstract:BACKGROUND & AIMS:In patients with cirrhosis and refractory ascites the role of beta-blockers in the development of paracentesis-induced circulatory dysfunction (PICD) is unknown. The aim of this study was to investigate the incidence of PICD before and after discontinuation of beta-blockers in patients with cirrhosis ...
journal_title:Journal of hepatology
pub_type: 临床试验,杂志文章
doi:10.1016/j.jhep.2011.01.034
更新日期:2011-10-01 00:00:00