Abstract:
BACKGROUND & AIMS:Hepatitis B virus (HBV) has developed strategies to evade immune responses. However, the mechanisms involved remain unclear. The NLRP3 inflammasome plays crucial roles in antiviral host defense and its downstream factor IL-1β has been shown to inhibit HBV infection in vivo. This study aims to assess whether HBV can affect the NLRP3 inflammasome signaling pathways and shed light on the underlying mechanisms HBV utilizes to evade host innate immune responses. METHODS:HBV inhibition of the lipopolysaccharide (LPS)-induced NLRP3 inflammasome activation was evaluated by Western blot, quantitative RT-PCR, flow cytometry and immunofluorescence. RESULTS:Kupffer cells expressed significantly more NLRP3 and IL-1β after LPS stimulation; whereas, chronic HBV infection suppressed LPS-induced NLRP3 and pro-IL-1β expression as well as IL-1β maturation. This inhibitory activity is mediated by HBeAg, and is involved in the inhibition of NF-κB signal pathway and reactive oxygen species (ROS) production. The inhibitory effect of HBeAg was confirmed in patients with chronic hepatitis B (CHB) and hepatocellular carcinoma by comparing the levels of IL-1β and NLRP3-related proteins in para-carcinoma tissues from HBeAg-positive or negative patients. Moreover, chronic HBV infection increases the susceptibility of mice to S. typhimurium infection, possibly via inhibiting the NLRP3 inflammasome activation and IL-1β production. CONCLUSIONS:HBeAg inhibits LPS-induced NLRP3 inflammasome activation and IL-1β production via suppressing NF-κB pathway and ROS production. This finding provides a novel mechanism for HBV-mediated suppression of innate immune responses, and identifies new therapeutic targets for chronic HBV infection and related diseases. LAY SUMMARY:HBeAg suppresses LPS-induced NLRP3 inflammasome activation and IL-1β production in two ways, one is to repress NLRP3 and pro-IL-1β expression via inhibiting NF-κB phosphorylation, and the other is to repress caspase-1 activation and IL-1β maturation via inhibiting ROS production. This effect contributes to the HBV persistence and immune tolerance.
journal_name
J Hepatoljournal_title
Journal of hepatologyauthors
Yu X,Lan P,Hou X,Han Q,Lu N,Li T,Jiao C,Zhang J,Zhang C,Tian Zdoi
10.1016/j.jhep.2016.12.018subject
Has Abstractpub_date
2017-04-01 00:00:00pages
693-702issue
4eissn
0168-8278issn
1600-0641pii
S0168-8278(16)30751-6journal_volume
66pub_type
杂志文章abstract:BACKGROUND/AIMS:In order to explore the role of cytokines in the pathogenesis of liver cirrhosis, we analyzed their gene expression in hepatic biopsies from patients with alcoholic liver cirrhosis, post-hepatitis C liver cirrhosis, and with idiopathic portal hypertension without cirrhosis. METHODS:We assessed the gene...
journal_title:Journal of hepatology
pub_type: 临床试验,杂志文章
doi:10.1016/s0168-8278(96)80140-1
更新日期:1996-05-01 00:00:00
abstract:BACKGROUND/AIMS:The finer branches of the biliary tree play an important role in biliary regeneration. They are consistently escorted by microvessels. Defects in the vascularization of these structures could impair bile duct regeneration. Therefore, we investigated the pattern of the escorting microvessels during the d...
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abstract:BACKGROUND/AIMS:Extrahepatic biliary atresia (EHBA) and chronic progressive intra-hepatic cholestasis (Byler's disease) are two distinct disorders of unknown etiology in the neonate, characterized by profound cholestasis. The aim of the present study was to investigate the inflammatory reaction in liver tissue from pat...
journal_title:Journal of hepatology
pub_type: 杂志文章
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doi:10.1016/s0168-8278(01)00177-5
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abstract::Hepatitis A virus (HAV) infection in adults is often symptomatic and disabling. The present article summarizes our experience with phase 2 studies of an inactivated hepatitis A virus vaccine. Pre- and post-exposure prophylaxis with immune globulin (IG) is only effective for 4-6 months. We compared the safety, tolerabi...
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pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1993-01-01 00:00:00
abstract:BACKGROUND/AIMS:Not all alcoholic patients develop severe liver disease with fibrosis progressing to cirrhosis. It is of practical importance to determine whether some markers can predict progression of liver fibrosis. METHODS:We used a baboon model that mimics human alcoholic liver disease. Cytokeratin 7 and 19 expre...
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更新日期:1996-03-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/s0168-8278(05)80058-3
更新日期:1994-02-01 00:00:00
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journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2008.10.028
更新日期:2009-03-01 00:00:00
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journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(05)80270-3
更新日期:1993-07-01 00:00:00
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doi:10.1016/j.jhep.2012.03.013
更新日期:2012-08-01 00:00:00
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更新日期:2012-03-01 00:00:00
abstract::Lactitol is a disaccharide analogue of lactulose which is available as a pure crystalline powder. The efficacy of lactitol in the treatment of chronic hepatic encephalopathy was assessed in 9 cirrhotic patients in a randomised, double-blind, cross-over comparison with lactulose. The sugars were dispensed in solutions,...
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(87)80086-7
更新日期:1987-04-01 00:00:00
abstract:BACKGROUND/AIMS:Primary sclerosing cholangitis (PSC) is associated with a high risk of cholangiocarcinoma. Our aim was to evaluate the diagnostic value of trypsinogen-1, trypsinogen-2, tumour-associated trypsin inhibitor, human chorionic gonadotropin beta and trypsin-2-alpha(1)-antitrypsin for cholangiocarcinoma and to...
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pub_type: 临床试验,杂志文章,多中心研究
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更新日期:2019-12-01 00:00:00
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journal_title:Journal of hepatology
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doi:10.1016/j.jhep.2004.04.015
更新日期:2004-08-01 00:00:00
abstract::Surveillance of patients at risk of developing hepatocellular carcinoma (HCC) is based on ultrasound (US) examinations performed at either 6 or 12 month intervals. Early detection of HCC in patients with cirrhosis is a challenging issue, since the different entities that are involved in the multi-step process of hepat...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2008.02.005
更新日期:2008-05-01 00:00:00
abstract:BACKGROUND/AIMS:To analyze the kinetics of the hepatitis C virus and the patterns of resistance to interferon alpha, we assessed HCV RNA levels early during retreatment with high-dose interferon in patients who did not respond to standard treatment. METHODS:Eleven non-responders to previous therapy with 3-6 MU interfe...
journal_title:Journal of hepatology
pub_type: 临床试验,杂志文章
doi:10.1016/s0168-8278(98)80343-7
更新日期:1998-06-01 00:00:00
abstract:BACKGROUND & AIMS:Blocking intestinal bile acid (BA) absorption by inhibiting or inactivating the apical sodium-dependent BA transporter (Asbt) classically induces hepatic BA synthesis. In contrast, blocking intestinal BA absorption by inactivating the basolateral BA transporter, organic solute transporter alpha-beta (...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2012.03.025
更新日期:2012-08-01 00:00:00
abstract:BACKGROUND/AIMS:The kinetics of omeprazole and its primary metabolites 5'-hydroxyomeprazole and omeprazole sulfone were studied in healthy volunteers to evaluate omeprazole as a probe drug for the S-mephenytoin hydroxylase (CYP2C19) polymorphism. The plasma metabolic ratio obtained from the concentrations of omeprazole...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:
更新日期:1995-09-01 00:00:00
abstract:BACKGROUND & AIMS:Liver transplantation is a recognized treatment for selected patients with hepatocellular carcinoma (HCC), but transplant criteria still need to be refined, especially in the case of more advanced or downstaged tumors. METHODS:The present study investigated alpha-fetoprotein (AFP) as a predictor of o...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2010.12.040
更新日期:2011-10-01 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
abstract::Hepatic fibrosis represents an important stage in the progression of chronic liver disease to cirrhosis. In the present paper we have investigated whether capsaicin-sensitive neuropeptide-containing sensory neurons may participate in the development of liver fibrosis. The expression of hepatic fibrosis induced by comm...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(90)90212-a
更新日期:1990-11-01 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:Von Willebrand factor (vWf) is found in high levels in plasma of patients with acute and chronic liver disease. The role of vWf in liver injury and repair is unknown. We studied the effect of liver mass and remodeling on plasma and tissue vWf after partial hepatectomy. METHODS:Rats were sacrificed post...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(02)00215-5
更新日期:2002-10-01 00:00:00