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TLR and hepatitis C

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https://www.readbyqxmd.com/read/29599452/direct-antiviral-properties-of-tlr-ligands-against-hbv-replication-in-immune-competent-hepatocytes
#1
Julie Lucifora, Marc Bonnin, Ludovic Aillot, Floriane Fusil, Sarah Maadadi, Laura Dimier, Maud Michelet, Océane Floriot, Anaïs Ollivier, Michel Rivoire, Malika Ait-Goughoulte, Stéphane Daffis, Simon P Fletcher, Anna Salvetti, François-Loïc Cosset, Fabien Zoulim, David Durantel
Current therapies for chronic hepatitis B virus (HBV) infections are effective at decreasing the viral load in serum, but do not lead to viral eradication. Recent studies highlighted the therapeutic or "adjuvant" potential of immune-modulators. Our aim was to explore the direct anti-HBV effect of Toll-Like-Receptors (TLR) agonists in hepatocytes. HBV-infected primary human hepatocytes (PHH) or differentiated HepaRG cells (dHepaRG) were treated with various TLR agonists. Amongst all TLR ligands tested, Pam3CSK4 (TLR1/2-ligand) and poly(I:C)-(HMW) (TLR3/MDA5-ligand) were the best at reducing all HBV parameters...
March 29, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29530841/tlr7-agonists-display-potent-antiviral-effects-against-norovirus-infection-via-innate-stimulation
#2
Daniel Enosi Tuipulotu, Natalie E Netzler, Jennifer H Lun, Jason M Mackenzie, Peter A White
Norovirus infections are a significant health and economic burden globally, accounting for hundreds of millions of cases of acute gastroenteritis every year. In the absence of an approved norovirus vaccine, there is an urgent need to develop antivirals to treat chronic infections and provide prophylactic therapy to limit viral spread during epidemics and pandemics. Toll-like receptor (TLR) agonists have been explored widely for their antiviral potential, and several are progressing through clinical trials for the treatment of human immunodeficiency virus (HIV) and hepatitis B virus (HBV) and as adjuvants for norovirus viruslike particle (VLP) vaccines...
May 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29475064/ursodeoxycholyl-lysophosphatidylethanolamide-negatively-regulates-tlr-mediated-lipopolysaccharide-response-in-human-thp-1-derived-macrophages
#3
Alzbeta Horvatova, Tanyarath Utaipan, Ann-Christin Otto, Yuling Zhang, Hongying Gan-Schreier, Petr Pavek, Anita Pathil, Wolfgang Stremmel, Walee Chamulitrat
The bile acid-phospholipid conjugate ursodeoxycholyl oleoyl-lysophophatidylethanolamide (UDCA-18:1LPE) is an anti-inflammatory and anti-fibrotic agent as previously shown in cultured hepatocytes and hepatic stellate cells as well as in in vivo models of liver injury. We hypothesize that UDCA-18:1LPE may directly inhibit the activation of immune cells. We found that UDCA-18:1LPE was capable of inhibiting the migration of phorbol ester-differentiated human THP-1 cells. We examined anti-inflammatory activity of UDCA-18:1LPE during activation of THP1-derived macrophages...
April 15, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29408639/hepatitis-b-virus-does-not-interfere-with-innate-immune-responses-in-the-human-liver
#4
Aleksei Suslov, Tujana Boldanova, Xueya Wang, Stefan Wieland, Markus H Heim
BACKGROUND & AIMS: Most viruses are detected at early stages of cell infection and induce an innate immune response mediated by production of interferons (IFNs). IFNs induce expression of hundreds of IFN-stimulated genes (ISGs). Infection of chimpanzees with hepatitis C virus, but not hepatitis B virus (HBV), induces ISG expression in the liver. HBV might not induce an innate immune response because it is not detected by pattern recognition receptors (the stealth properties of HBV) or because HBV suppresses IFN production or signaling despite detection by pattern recognition receptors...
May 2018: Gastroenterology
https://www.readbyqxmd.com/read/29350750/the-hepatoprotective-effect-of-selenium-enriched-yeast-and-gum-arabic-combination-on-carbon-tetrachloride-induced-chronic-liver-injury-in-rats
#5
Mohammed Hamid, Yassin Abdulrahim, Dandan Liu, Gang Qian, Alamzeb Khan, Kehe Huang
The antioxidant and anti-inflammatory effects of selenium-enriched yeast (SY) and Gum Arabic (GA) have been reported. This study aimed to determine the hepatoprotective effect of SY and GA combination on carbon tetrachloride (CCl4 )-induced chronic liver injury in rats and to explore their synergistic mechanisms of action. Forty adult male Wistar rats randomly allotted to 5 groups: (A) worked as control, (B) was administered CCl4 , (C-E) were fed daily by GA, SY, and GA+SY respectively after mixing with basal diet, following CCl4 -intoxication...
February 2018: Journal of Food Science
https://www.readbyqxmd.com/read/29276096/the-association-of-variations-in-tlr-genes-and-spontaneous-immune-control-of-hepatitis-b-virus
#6
Seyma Katrinli, Adil Nigdelioglu, Kamil Ozdil, Gizem Dinler-Doganay, Levent Doganay
BACKGROUND: Toll-like receptors (TLRs) are suspected to play a critical role in liver diseases and the progression of chronic hepatitis B (CHB) infection. In this study, we investigated the possible association between TLRs and hepatitis B virus (HBV) infection chronicity in Turkish population. METHODS: TLR4 (+896 A→G) (rs4986790), TLR5 (+1846 T→C) (rs5744174) and TLR9 (-1237T→C) (rs5743836) polymorphisms were screened in 131 CHB patient and 168 individuals by polymerase chain reaction (PCR) - restriction fragment length polymorphism (RFLP) technique...
December 21, 2017: Clinics and Research in Hepatology and Gastroenterology
https://www.readbyqxmd.com/read/29217822/hepatocyte-toll-like-receptor-4-mediates-lipopolysaccharide-induced-hepcidin-expression
#7
Yong-Soo Lee, Yong-Hoon Kim, Yoon Seok Jung, Ki-Sun Kim, Don-Kyu Kim, Soon-Young Na, Ji-Min Lee, Chul-Ho Lee, Hueng-Sik Choi
Hepcidin expression is induced by inflammatory molecules such as lipopolysaccharide (LPS) via a macrophage-mediated pathway. Although hepatocytes directly respond to LPS, the molecular mechanism underlying toll-like receptor (TLR)-dependent hepcidin expression by hepatocytes is mostly unknown. Here we show that LPS can directly induce the mRNA expression and secretion of hepcidin by hepatocytes via TLR4 activation. Using hepatocytes deficient in TLR4, myeloid differentiation factor 88 (MyD88) and TIR domain-containing adaptor inducing interferon-β (TRIF), we demonstrated that LPS-induced hepcidin expression by hepatocytes is regulated by its specific receptor, TLR4, via a MyD88-dependent signaling pathway...
December 8, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29079574/interferon-regulatory-factor-5-irf5-suppresses-hepatitis-c-virus-hcv-replication-and-hcv-associated-hepatocellular-carcinoma
#8
Ozge Cevik, Dan Li, Erdene Baljinnyam, Dinesh Manvar, Erica M Pimenta, Gulam Waris, Betsy J Barnes, Neerja Kaushik-Basu
Hepatitis C virus (HCV) infection is a major risk factor for the development of chronic liver disease. The disease typically progresses from chronic HCV to fibrosis, cirrhosis, hepatocellular carcinoma (HCC), and death. Chronic inflammation associated with HCV infection is implicated in cirrhosis and HCC, but the molecular players and signaling pathways contributing to these processes remain largely unknown. Interferon regulatory factor 5 (IRF5) is a molecule of interest in HCV-associated HCC because it has critical roles in virus-, Toll-like receptor (TLR)-, and IFN-induced signaling pathways...
December 29, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28972610/fat-1-mice-prevent-high-fat-plus-high-sugar-diet-induced-non-alcoholic-fatty-liver-disease
#9
Xiao-Fei Guo, Jin-Long Gao, Jiao-Mei Li, Duo Li
High-fat and high-sugar (HFS) diets have been suggested to play a causal role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). This study aimed to investigate whether fat-1 transgenic mice with a higher tissue content of n-3 polyunsaturated fatty acids (PUFAs) could prevent HFS diet-induced NAFLD, compared with wild-type mice. The fat-1 and wild-type littermates had free access to a 15% fructose solution plus high-fat diet, a 15% glucose solution plus high-fat diet, or a 15% sucrose solution plus high-fat diet, respectively...
October 3, 2017: Food & Function
https://www.readbyqxmd.com/read/28963016/delivery-of-the-tlr-ligand-poly-i-c-to-liver-cells-in-vitro-and-in-vivo-by-calcium-phosphate-nanoparticles-leads-to-a-pronounced-immunostimulation
#10
Viktoriya Sokolova, Zou Shi, Shunmei Huang, Yanqin Du, Mathis Kopp, Annika Frede, Torben Knuschke, Jan Buer, Dongliang Yang, Jun Wu, Astrid Maria Westendorf, Matthias Epple
The selective activation of the immune system is a concurrent problem in the treatment of persistent diseases like viral infections (e.g. hepatitis). For the delivery of the toll-like receptor ligand poly(I:C), an immunostimulatory action was discovered earlier by hydrodynamic injection. However, this technique is not clinically transferable to human patients. A modular system where the immunoactive toll-like-receptor ligand 3 (TLR-3) poly(I:C) was incorporated into calcium phosphate nanoparticles was developed...
December 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28924346/co-delivery-of-polyinosinic-polycytidylic-acid-and-flagellin-by-poly-lactic-co-glycolic-acid-mps-synergistically-enhances-immune-response-elicited-by-intranasally-delivered-hepatitis-b-surface-antigen
#11
Xiaojing Dai, Jintian He, Ruxia Zhang, Guanghao Wu, Fangfang Xiong, Baohua Zhao
The aim of the present work was to investigate the synergistic effect between toll-like receptor (TLR) 3 ligand polyinosinic:polycytidylic acid (pI:C) and TLR5 ligand flagellin (FLN) on immune responses induced by nasally delivered hepatitis B virus surface antigen (HBsAg). Mannan and chitosan oligosaccharide-modified, pH-responsive poly(lactic- co -glycolic acid) (MC-PLGA) microparticles (MPs) containing HBsAg, FLN, pI:C or both ligands were prepared with a double-emulsion method. In vitro uptake experiments show that cellular uptake of MC-PLGA MPs by macrophages was through energy-dependent, receptor-mediated endocytosis mechanism...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28790196/trif-dependent-toll-like-receptor-signaling-suppresses-scd1-transcription-in-hepatocytes-and-prevents-diet-induced-hepatic-steatosis
#12
Jing Chen, Jin Li, Jensen H C Yiu, Jenny K W Lam, Chi-Ming Wong, Bernhard Dorweiler, Aimin Xu, Connie W Woo
Nonalcoholic fatty liver disease (NAFLD) includes a spectrum of diseases that ranges in severity from hepatic steatosis to steatohepatitis, the latter of which is a major predisposing factor for liver cirrhosis and cancer. Toll-like receptor (TLR) signaling, which is critical for innate immunity, is generally believed to aggravate disease progression by inducing inflammation. Unexpectedly, we found that deficiency in TIR domain-containing adaptor-inducing interferon-β (TRIF), a cytosolic adaptor that transduces some TLR signals, worsened hepatic steatosis induced by a high-fat diet (HFD) and that such exacerbation was independent of myeloid cells...
August 8, 2017: Science Signaling
https://www.readbyqxmd.com/read/28687713/tlr9-is-up-regulated-in-human-and-murine-nash-pivotal-role-in-inflammatory-recruitment-and-cell-survival
#13
Auvro R Mridha, Fahrettin Haczeyni, Matthew M Yeh, W Geoffrey Haigh, George N Ioannou, Vanessa Barn, Hussam Ajamieh, Leon Adams, Jeffrey M Hamdorf, Narci C Teoh, Geoffrey C Farrell
Background and aims: TLR9 deletion protects against steatohepatitis due to choline-amino acid depletion and high-fat diet. We measured TLR9 in human non-alcoholic steatohepatitis (NASH) livers, and tested whether TLR9 mediates inflammatory recruitment in three murine models of non-alcoholic fatty liver disease (NAFLD). Methods: We assayed TLR mRNA in liver biopsies from bariatric surgery patients. Wild-type (Wt), appetite-dysregulated Alms1 mutant (foz/foz), Tlr9(-/-), and Tlr9(-/-)foz/foz C57BL6/J mice and bone marrow (BM) chimeras were fed 0...
August 15, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28654793/pure-total-flavonoids-from-citrus-improve-non-alcoholic-fatty-liver-disease-by-regulating-tlr-ccl-signaling-pathway-a-preliminary-high-throughput-omics-study
#14
Liyan Wu, Maoxiang Yan, Jianping Jiang, Beihui He, Wei Hong, Zhiyun Chen
OBJECTIVE: This study investigated the possible molecular mechanisms of pure total flavonoids from citrus (PTFC) for the treatment of non-alcoholic fatty liver disease (NAFLD) via toll-like receptor/C-C chemokine ligand (TLR/CCL) signaling pathways by monitoring the changes in gene expression profile in liver tissues induced by high-fat diet. METHODS: We performed systematical analyses on hepatic expression profiles of mRNAs in a high-fat diet (HFD)-induced steatotic animal model with or without PTFC treatment...
September 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28551415/interferon-%C3%AE-response-is-impaired-by-hepatitis-b-virus-infection-in-tupaia-belangeri
#15
Mohammad Enamul Hoque Kayesh, Sayeh Ezzikouri, Haiying Chi, Takahiro Sanada, Naoki Yamamoto, Bouchra Kitab, Takumi Haraguchi, Rika Matsuyama, Chimène Nze Nkogue, Hitoshi Hatai, Noriaki Miyoshi, Shuko Murakami, Yasuhito Tanaka, Jun-Ichiro Takano, Yumiko Shiogama, Yasuhiro Yasutomi, Michinori Kohara, Kyoko Tsukiyama-Kohara
To date, the chimpanzee has been used as the natural infection model for hepatitis B virus (HBV). However, as this model is very costly and difficult to use because of ethical and animal welfare issues, we aimed to establish the tupaia (Tupaia belangeri) as a new model for HBV infection and characterized its intrahepatic innate immune response upon HBV infection. First, we compared the propagation of HBV genotypes A2 and C in vivo in tupaia hepatocytes. At 8-10days post infection (dpi), the level of HBV-A2 propagation in the tupaia liver was found to be higher than that of HBV-C...
June 2, 2017: Virus Research
https://www.readbyqxmd.com/read/28521532/new-antivirals-for-the-treatment-of-chronic-hepatitis-b
#16
REVIEW
Vincent Soriano, Pablo Barreiro, Laura Benitez, Jose M Peña, Carmen de Mendoza
Current treatment with oral nucleos(t)ides entecavir or tenofovir provide sustained suppression of HBV replication and clinical benefit in most chronic hepatitis B virus (HBV) infected persons. However, HBV rebound generally occurs upon drug discontinuation due to persistence of genomic HBV reservoirs as episomic cccDNA and chromosomic integrated HBV-DNA. There is renewed enthusiasm on HBV drug discovery following recent successes with antivirals for hepatitis C and immunotherapies for some cancers. Areas covered: New drugs that target distinct steps of the HBV life cycle are been developed, including inhibitors of viral entry, new polymerase inhibitors, capsid and assembly inhibitors, virus release blockers, and disruptors of cccDNA formation and transcription...
July 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28093541/association-of-toll-like-receptor-3-and-toll-like-receptor-9-single-nucleotide-polymorphisms-with-hepatitis-c-virus-infection-and-hepatic-fibrosis-in-egyptian-patients
#17
Rania A Zayed, Dalia Omran, Doha A Mokhtar, Zinab Zakaria, Sameera Ezzat, Mohamed A Soliman, Lamiaa Mobarak, Hossam El-Sweesy, Ghada Emam
AbstractToll-like receptors (TLRs) are recognized as fundamental contributors to the immune system function against infections. Hepatitis C virus (HCV) infection represents a global health problem especially in Egypt having the highest HCV prevalence worldwide where HCV infection is a continuing epidemic. The aim of the present study was to investigate the possible association between genetic variation in TLR-3 and TLR-9 and HCV infection and hepatic fibrosis in chronic HCV-positive Egyptian patients. The present study included 100 naïve chronic HCV-positive patients and 100 age- and sex-matched healthy controls...
March 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/27910749/role-of-toll-like-receptors-in-hepatitis-c-virus-pathogenesis-and-treatment
#18
REVIEW
Usman Ali Ashfaq, Muhammad Sarfaraz Iqbal, Saba Khaliq
Viral infections are rising every day, and viruses appear to be the most dangerous pathogens in the world. Hepatitis C virus (HCV) is accepted as one of the major destructive factors of promoting severe hepatic disorders by infecting more than 180 million individuals throughout the world. Chronic infection caused by HCV poses a serious global health emergency and appears to be a powerful threat to humanity. Almost 20 years have passed since the disclosure of HCV, but even now, treatment preferences remain limited...
2016: Critical Reviews in Eukaryotic Gene Expression
https://www.readbyqxmd.com/read/27796312/ubc13-haploinsufficiency-protects-against-age-related-insulin-resistance-and-high-fat-diet-induced-obesity
#19
Erina Joo, Toru Fukushima, Norio Harada, John C Reed, Shu-Ichi Matsuzawa, Nobuya Inagaki
Obesity is associated with low-grade inflammation that leads to insulin resistance and type 2 diabetes via Toll-like Receptor (TLR) and TNF-family cytokine receptor (TNFR) signaling pathways. Ubc13 is an ubiquitin-conjugating enzyme responsible for non-canonical K63-linked polyubiquitination of TNF receptor-associated factor (TRAF)-family adapter proteins involved in TLR and TNFR pathways. However, the relationship between Ubc13 and metabolic disease remains unclear. In this study, we investigated the role of Ubc13 in insulin resistance and high-fat diet (HFD)-induced obesity...
October 31, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27681126/suppression-of-host-innate-immune-response-by-hepatitis-c-virus-via-induction-of-autophagic-degradation-of-traf6
#20
Stephanie T Chan, Jiyoung Lee, Mansi Narula, J-H James Ou
Tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6) is an important adaptor molecule that mediates the TNFR family and interleukin-1 (IL-1)/Toll-like receptor (TLR) signaling cascades. These pathways are important for the host to control viral infections. In this report, we demonstrated that hepatitis C virus (HCV) depleted TRAF6 from its host cells through a posttranslational mechanism. This depletion was independent of proteasomes, as it was not affected by the proteasome inhibitor MG132, but it was suppressed by bafilomycin A1, which led to the association of TRAF6 with autophagosomes...
December 1, 2016: Journal of Virology
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