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Tlr4 liver

Lei Liang, Xue Yang, Yang Yu, Xiaoyong Li, Yechen Wu, Rongyu Shi, Jinghua Jiang, Lu Gao, Fei Ye, Qiudong Zhao, Rong Li, Lixin Wei, Zhipeng Han
Babao Dan (BBD), a traditional Chinese medicine, has been widely used as a complementary and alternative medicine to treat chronic liver diseases. In this study, we aimed to observe the protective effect of BBD on rat hepatic fibrosis induced by diethylnitrosamine (DEN) and explore it possible mechanism. BBD was administrated while DEN was given. After eight weeks, values of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) indicated that BBD significantly protected liver from damaging by DEN and had no obvious side effect on normal rat livers...
October 20, 2016: Oncotarget
Ra-Yeong Choi, Ju Ri Ham, Mi-Kyung Lee
This study investigated the effects and mechanism of esculetin (6,7-dihydroxycoumarin) on non-alcoholic fatty liver in diabetic mice fed high-fat diet (HFD). The diabetic mice model was induced by injection of streptozotocin, after which they were fed HFD diet with or without esculetin for 11 weeks. Non-diabetic mice were provided a normal diet. Diabetes induced hepatic hypertrophy, lipid accumulation and droplets; however, esculetin reversed these changes. Esculetin treatment in diabetic mice fed HFD significantly down-regulated expression of lipid synthesis genes (Fasn, Dgat2 and Pap) and inflammation genes (Tlr4, Myd88, Nfkb, Tnfα and Il6)...
October 18, 2016: Chemico-biological Interactions
Gemma Odena, Jiegen Chen, Juan Jose Lozano, Jose Altamirano, Daniel Rodrigo-Torres, Silvia Affo, Oriol Morales-Ibanez, Hiroshi Matsushita, Jian Zou, Raluca Dumitru, Juan Caballeria, Pere Gines, Vicente Arroyo, Min You, Pierre-Emmanuel Rautou, Dominique Valla, Fulton Crews, Ekihiro Seki, Pau Sancho-Bru, Ramon Bataller
Alcoholic hepatitis (AH) is the most severe form of alcoholic liver disease for which there are no effective therapies. Patients with AH show impaired hepatocyte proliferation, expansion of inefficient ductular cells and high lipopolysaccharide (LPS) levels. It is unknown whether LPS mediates ductular cell expansion. We performed transcriptome studies and identified keratin 23 (KRT23) as a new ductular cell marker. KRT23 expression correlated with mortality and LPS serum levels. LPS-TLR4 pathway role in ductular cell expansion was assessed in human and mouse progenitor cells, liver slices and liver injured TLR4 KO mice...
October 18, 2016: Scientific Reports
Shu-Jing Yu, Rong Jiang, Ying Z Mazzu, Cai-Bing Wei, Zong-Liang Sun, Yu-Zhen Zhang, Lian-Di Zhou, Qi-Hui Zhang
Drug-induced liver injury (DILI) is the most common cause of acute liver failure. Disruption of the Th17/Treg balance can lead to hepatic inflammation, which causes the main symptoms of DILI. Here we investigate the protective mechanisms of (-)-Epigallocatechin-3-gallate (EGCG) on triptolide (TP)-induced DILI that shows the Th17/Treg imbalance. Pretreatment with EGCG (5[Formula: see text]mg/kg) for 10 days before TP (0.5[Formula: see text]mg/kg) administration in mice significantly reduced the increased alanine aminotransferase (ALT) level ([Formula: see text]) induced by TP treatment...
2016: American Journal of Chinese Medicine
Juneo F Silva, Natália M Ocarino, Rogéria Serakides
The gene and/or protein expression of proteases and immunological, angiogenic, hormonal and apoptotic mediators was evaluated in rat placenta before and during intrauterine trophoblast migration. The depth of interstitial and endovascular intrauterine trophoblast invasion and the immunohistochemical expression of vascular endothelial growth factor (VEGF), fetal liver kinase 1 (Flk1), interferon (IFN)-γ, migration inhibitory factor (MIF), and inducible nitric oxide synthase (iNOS; also known as nitric oxide synthase (NOS) 2) were evaluated...
October 14, 2016: Reproduction, Fertility, and Development
Zigong Shao, Baoping Jiao, Tingting Liu, Ying Cheng, Hao Liu, Yongfeng Liu
OBJECTIVES: This study aims to test the effects of TAK-242 on liver transplant viability in a model of swine Maastricht-category-III cardiac death. METHODS: A swine DCD Maastricht-III model of cardiac death was established, and TAK-242 was administered prior to the induction of cardiac death. The protein and mRNA level of TLR4 signaling pathway molecules and cytokines that are important in mediating immune and inflammatory responses were assessed at different time points following the induction of cardiac death...
September 26, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Rong Li, Jianhua Song, Wei Wu, Xinmou Wu, Min Su
In this study, we aim to explore the potential benefits of puerarin on metabolic function of liver fibrosis (LF) rat induced by carbon tetrachloride (CCl4), and to investigate with the underlying molecular mechanism targeted on liver and pancreas tissues. In methodology, The LF rats were prepared through intragastrically giving CCl4 twice each week (2ml/kg, v/w) for 8weeks, and dosed puerarin (20, 40mg/kg) were given three times each week via intraperitoneal injection. After being conducted with oral glucose tolerance test (OGTT), the blood samples of rat were harvested for biochemical tests, as well as the liver and pancreas were isolated for histological examination and biochemical assays...
September 24, 2016: Gene
Yasodha Krishnasamy, Venkat K Ramshesh, Monika Gooz, Rick G Schnellmann, John J Lemasters, Zhi Zhong
BACKGROUND AND AIM: Because ethanol consumption is commonly associated with a high cholesterol diet, we examined whether combined consumption of ethanol and high cholesterol increases liver injury and fibrosis. METHODS: Male C57BL/6J mice were fed diets containing: 1) 35% of calories from corn oil (CTR), 2) CTR plus 0.5% (w/v) cholesterol (Chol), 3) CTR plus ethanol (27% of calories) (EtOH), or 4) EtOH+Chol for 3 months. RESULTS: In mice fed Chol or EtOH alone, ALT increased to ~160 U/L, moderate hepatic steatosis occurred, and leukocyte infiltration, necrosis, and apoptosis increased modestly, but no observable fibrosis developed...
2016: PloS One
Purnima Gupta, Supriya Srivastav, Shriya Saha, Pijush K Das, Anindita Ukil
In order to establish infection, intra-macrophage parasite Leishmania donovani needs to inhibit host defense parameters like inflammatory cytokine production and apoptosis. In the present study, we demonstrate that the parasite achieves both by exploiting a single host regulator AKT for modulating its downstream transcription factors, β-catenin and FOXO-1. L. donovani-infected RAW264.7 and bone marrow-derived macrophages (BMDM) treated with AKT inhibitor or dominant negative AKT constructs showed decreased anti-inflammatory cytokine production and increased host cell apoptosis resulting in reduced parasite survival...
November 1, 2016: Cell Death and Differentiation
Uzma Malik, Aneela Javed
Mammalian immune system is a complex amalgam of diverse cellular and noncellular components such as cytokines, receptors and co-receptors. FAM26F (family with sequence similarity 26, member F) is a recently identified tetraspanin-like membrane glycoprotein which is predicted to make homophilic interactions and potential synapses between several immune cells including CD4(+), CD8(+), NK, dendritic cells and macrophages. Various whole transcriptome analyses have demonstrated the differential expression of FAM26F in several bacterial, viral and parasitic infections, in certain pathophysiological conditions such as liver and heart transplantation, and in various cancers...
September 19, 2016: International Reviews of Immunology
Muhamad Marlini, Ayako Mabuchi, Beth L Mallard, Ngatiman Hairulhisyam, Sachiko Akashi-Takamura, Jacquie L Harper, Antony M Wheatley
Liver regeneration is delayed in mice with a defective TLR4 (C3H/HeJ) but is normal in TLR4 knockouts (TLR4(-/-) ). Here, we investigated the possible involvement of structural and hemodynamic changes in vivo in the underlying mechanism. In LPS-sensitive (C3H/HeN, C57BL/6) and LPS-insensitive (C3H/HeJ, TLR4(-/-) ) mice, a 70% partial hepatectomy (PH) was performed under inhalational anesthesia. At days 3 and 7 after PH, the hepatic microcirculation was interrogated using intravital microscopy. Delayed liver regeneration was confirmed in C3H/HeJ, but not in C3H/HeN, C57BL/6 (WT) or TLR4(-/-) mice by liver weight-to-body-weight ratio, percentage of PCNA-positive cells and mitotic index data...
September 16, 2016: Experimental Physiology
Romina Fiorotto, Ambra Villani, Antonis Kourtidis, Roberto Scirpo, Mariangela Amenduni, Peter J Geibel, Massimilano Cadamuro, Carlo Spirli, Panos Z Anastasiadis, Mario Strazzabosco
: In the liver, CFTR regulates bile secretion and other functions at the apical membrane of biliary epithelial cells (i.e cholangiocytes). CF-related liver disease (CFLD) is a major cause of death in patients with CF. CFTR dysfunction affects innate immune pathways, generating a para-inflammatory status in the liver, and other epithelia. This study investigates the mechanisms linking CFTR to TLR4 activity. We found that CFTR is associated in a multi-protein complex at the apical membrane of normal mouse cholangiocytes, with proteins that negatively control Src activity...
September 15, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Nya L Fraleigh, Justin Boudreau, Nitin Bhardwaj, Nelson F Eng, Yanal Murad, Robert Lafrenie, Reinaldo Acevedo, Reynaldo Oliva, Francisco Diaz-Mitoma, Hoang-Thanh Le
Tobacco smoking is recognized as a global pandemic resulting in 6 million deaths per year. Despite a variety of anti-smoking products available to aid with tobacco cessation, the majority of people who attempt to quit smoking relapse within 6 months due to the addictive nature of nicotine. An immunotherapy approach could offer a promising treatment option by inducing a potent selective antibody response against nicotine in order to block its distribution to the brain and its addictive effects in the central nervous system...
August 2016: Heliyon
Marcos Vasquez, Jessica Fioravanti, Fernando Aranda, Vladimir Paredes, Celia Gomar, Nuria Ardaiz, Veronica Fernandez-Ruiz, Miriam Méndez, Estanislao Nistal-Villan, Esther Larrea, Qinshan Gao, Gloria Gonzalez-Aseguinolaza, Jesus Prieto, Pedro Berraondo
Scavenger receptor class B type I (SR-B1) binds pathogen-associated molecular patterns participating in the regulation of the inflammatory reaction but there is no information regarding potential interactions between SR-B1 and the interferon system. Herein, we report that SR-B1 ligands strongly regulate the transcriptional response to interferon α (IFNα) and enhance its antiviral and antitumor activity. This effect was mediated by the activation of TLR2 and TLR4 as it was annulled by the addition of anti-TLR2 or anti-TLR4 blocking antibodies...
August 2016: Oncoimmunology
Shannon L Glisan, Caroline Ryan, Andrew P Neilson, Joshua D Lambert
Cranberry (Vaccinium macrocarpon) consumption has been associated with health beneficial effects. Nonalcoholic fatty liver disease (NAFLD) is a comorbidity of obesity. In the present study, we investigated the effect of a polyphenol-rich cranberry extract (CBE) on hepatic inflammation in high fat (HF)-fed obese C57BL/6J mice. Following dietary treatment with 0.8% CBE for 10 weeks, we observed no change in body weight or visceral fat mass in CBE-supplemented mice compared to HF-fed control mice. We did observe a significant decrease in plasma alanine aminotransferase (31%) and histological severity of NAFLD (33% decrease in area of involvement, 29% decrease in lipid droplet size) compared to HF-fed controls...
August 4, 2016: Journal of Nutritional Biochemistry
Yuehua Wang, Bin Li, Jinyan Zhu, Qi Zhang, Xiuyan Zhang, Li Li, Yan Ma, Xianjun Meng
The protective effects of Lonicera caerulea berry extract (LCBE) against hepatic inflammation and the underlying mechanisms were investigated in a rat model of lipopolysaccharide (LPS)-induced chronic liver inflammation. Male Sprague-Dawley rats were injected with LPS (200 μg per kg bw) with or without LCBE co-administration (50, 100 and 200 mg per kg bw intragastrically once daily) for 4 weeks. We found that LCBE supplementation inhibited the increase in Toll-like receptor (TLR)2 and TLR4 expression induced by LPS, while preventing glutathione depletion and reactive oxidative species generation and abrogating increases in C-reactive protein and interleukin-6 levels, restoring alanine and aspartate aminotransferase activities, and blocking the phosphorylation of p38 and c-Jun N-terminal kinase mitogen-activated protein kinases (MAPKs)...
October 12, 2016: Food & Function
Xi Li, Qianwen Jin, Qunyan Yao, Beili Xu, Zheng Li, Chuantao Tu
This study aimed to investigate the effects of quercetin on liver fibrogenesis in mice and to elucidate the underlying molecular mechanisms. Mice were administered with carbon tetrachloride (CCl4) for eight weeks to induce liver fibrosis and concomitantly orally treated with quercetin (50mgkg(-1)day(-1)). Here, we demonstrated that quercetin dramatically ameliorated liver injury, inflammation, and hepatic fibrogenesis induced by CCl4. Quercetin also inhibited the activation of hepatic stellate cells (HSC) in vivo and in vitro, as evaluated by α-smooth muscle actin (α-SMA) expression, which is a specific marker of HSC activation...
November 2, 2016: Toxicology Letters
Haojun Yang, Haoming Zhou, Lin Zhuang, Xuehao Wang, Ling Lv
BACKGROUND: The G protein-coupled receptor TGR5 is a novel plasma membrane-bound G protein-coupled bile acid (BA) receptor. TGR5-induced liver protection has been demonstrated during several liver diseases, except during ischemia/reperfusion injury (IRI). METHOD: Male adult wild-type and TGR5 knockout mice were subjected to liver partial warm ischemia/reperfusion. Hepatic injury was evaluated based on serum alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST)...
September 6, 2016: Liver Transplantation
Rui Guo, Bin Lin, Jing Fei Pan, Emily C Liong, Ai Min Xu, Moussa Youdim, Man Lung Fung, Kwok Fai So, George L Tipoe
Acute liver disease is characterized by inflammation, oxidative stress and necrosis, which can greatly influence the long term clinical outcome and lead to liver failure or cancer. Here, we initially demonstrated the beneficial role of caspase-9-dependent autophagy in acute liver injury. Treatment with caspase-9 inhibitor z-LEHD-FMK in HepG2 cells, AML12 cells and C57BL/b6N mice exacerbated CCl4-induced acute hepatocellular damage, and also down-regulated autophagy markers expression levels, indicating that caspase-9 inhibition may aggravate acute liver damage by suppressing cytoprotective autophagy...
2016: Scientific Reports
In Hee Kim, Jun Xu, Xiao Liu, Yukinori Koyama, Hsiao-Yen Ma, Karin Diggle, Young-Hyun You, Jan M Schilling, Dilip Jeste, Kumar Sharma, David A Brenner, Tatiana Kisseleva
We aimed to investigate whether aging increases the susceptibility of hepatic and renal inflammation or fibrosis in response to high-fat diet (HFD) and explore the underlying genetic alterations. Middle (10 months old) and old (20 months old) aged, male C57BL/6N mice were fed either a low-fat diet (4 % fat) or HFD (60 % fat) for 4 months. Young (3 months old) aged mice were included as control group. HFD-induced liver and kidney injuries were analyzed by serum and urine assay, histologic staining, immunohistochemistry, and reverse-transcription real-time quantitative polymerase chain reaction...
August 2016: Age (2005-)
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