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Tlr4 liver

Haoming Zhou, Han Wang, Ming Ni, Shi Yue, Yongxiang Xia, Ronald W Busuttil, Jerzy W Kupiec-Weglinski, Ling Lu, Xuehao Wang, Yuan Zhai
BACKGROUND & AIMS: Glycogen synthase kinase 3β (Gsk3β) is a ubiquitously expressed kinase with distinctive functions in different types of cells. Although its roles in regulating innate immune activation and ischemia and reperfusion injuries (IRI) have been well documented, underlying mechanisms remain ambiguous, due in part to the lack of cell-specific tools in vivo. METHODS: We created a myeloid-specific Gsk3β KO strain to study its function in macrophages in a murine liver partial warm ischemia model...
February 13, 2018: Journal of Hepatology
Wei He, Ting Yuan, Dolma Choezom, Hannah Hunkler, Karthika Annamalai, Blaz Lupse, Kathrin Maedler
Ageing and obesity are two major risk factors for the development of type 2 diabetes (T2D). A chronic, low-grade, sterile inflammation contributes to insulin resistance and β-cell failure. Toll-like receptor-4 (TLR4) is a major pro-inflammatory pathway; its ligands as well as downstream signals are increased systemically in patients with T2D and at-risk individuals. In the present study we investigated the combined effects of high fat/high sucrose diet (HFD) feeding, ageing and TLR4-deficiency on tissue inflammation, insulin resistance and β-cell failure...
February 9, 2018: Scientific Reports
Yuanyuan Wu, Yujing Shao, Bochen Song, Wenrui Zhen, Zhong Wang, Yuming Guo, Muhammad Suhaib Shahid, Wei Nie
Background: The poultry industry is in need of effective antibiotic alternatives to control outbreaks of necrotic enteritis (NE) due to Clostridium perfringens. Methods: This study was conducted to investigate the effects of feeding Bacillus coagulans on the growth performance and gut health of broiler chickens with C. perfringens-induced NE. Two hundred and forty 1-day-old broiler chicks were randomly assigned to a 2 × 2 factorial arrangement with two dietary B...
2018: Journal of Animal Science and Biotechnology
Ya-Nan Jia, Hai-Peng Lu, Ya-Lin Peng, Bao-Shun Zhang, Xiao-Bao Gong, Jun Su, You Zhou, Min-Hui Pan, Li Xu
Oxyresveratrol (Oxy) is a natural polyhydroxystilbene abundant in mulberry that has anti-inflammation and anti-oxidant activities. We evaluated the protective effect of Oxy in the context of the lipopolysaccharide and d-galactosamine (LPS/d-GalN) induced acute liver injury. Oxy restricted the development of histopathological changes, markedly reduced the activity of alanine transaminase (ALT) and aspartate transaminase (AST), which are indicators of impaired liver function. Oxy significantly regulated the contents of oxidative stress related enzymes and products, and inhibited expressions of inflammatory mediators and cytokines...
January 23, 2018: International Immunopharmacology
Young-Sun Lee, Doyeon Kim, Tae-Jun Kim, So Yeon Kim, Jae-Kwang Jung, Jae-Kap Choi, Hyon-Seung Yi, Jin-Seok Byun
The importance of toll-like receptor (TLR) 4 has been well documented in pathogenesis of steatohepatitis, however, little is known about the role of TLR3. In this study, we investigated whether the depletion of TLR3 modulate the hepatic injury in mice, and further try to provide mechanistic insight of TLR3-mediated modulation from diet-induced hepatic inflammation and fat accumulation. Hepatic steatosis and inflammatory response were developed by feeding wild type (WT) or TLR3 knockout mice with high-fat diet for 8 weeks...
February 1, 2018: Biochemical and Biophysical Research Communications
Xia Wu, Jessica B Roberto, Allison Knupp, Heidi L Kenerson, Camtu D Truong, Sebastian Y Yuen, Katherine J Brempelis, Marianne Tuefferd, Antony Chen, Helen Horton, Raymond S Yeung, Ian N Crispe
The liver is the central metabolic organ in the human body, and also plays an essential role in innate and adaptive immunity. While mouse models offer significant insights into immune-inflammatory liver disease, human immunology differs in important respects. It is not easy to address those differences experimentally. Therefore, to improve the understanding of human liver immunobiology and pathology, we have established precision-cut human liver slices to study innate immunity in human tissue. Human liver slices collected from resected livers could be maintained in ex vivo culture over a two-week period...
January 31, 2018: Journal of Immunological Methods
Meng-Ping Jiang, Chun Xu, Yun-Wei Guo, Qian-Jiang Luo, Lin Li, Hui-Ling Liu, Jie Jiang, Hui-Xin Chen, Xiu-Qing Wei
AIM: To study the role and the possible mechanism of β-arrestin 2 in lipopolysaccharide (LPS)-induced liver injury in vivo and in vitro. METHODS: Male β-arrestin 2+/+ and β-arrestin 2-/- C57BL/6J mice were used for in vivo experiments, and the mouse macrophage cell line RAW264.7 was used for in vitro experiments. The animal model was established via intraperitoneal injection of LPS or physiological sodium chloride solution. Blood samples and liver tissues were collected to analyze liver injury and levels of pro-inflammatory cytokines...
January 14, 2018: World Journal of Gastroenterology: WJG
Maria J Perugorria, Aitor Esparza-Baquer, Fiona Oakley, Ibone Labiano, Ana Korosec, Alexander Jais, Jelena Mann, Dina Tiniakos, Alvaro Santos-Laso, Ander Arbelaiz, Riem Gawish, Ana Sampedro, Antonio Fontanellas, Elizabeth Hijona, Raul Jimenez-Agüero, Harald Esterbauer, Dagmar Stoiber, Luis Bujanda, Jesus María Banales, Sylvia Knapp, Omar Sharif, Derek A Mann
OBJECTIVE: Liver injury impacts hepatic inflammation in part via Toll-like receptor (TLR) signalling. Triggering receptor expressed on myeloid cells 2 (TREM-2) modulates TLR4-mediated inflammation in bone marrow (BM)-derived macrophages but its function in liver injury is unknown. Here we hypothesised that the anti-inflammatory effects of TREM-2 on TLR signalling may limit hepatic injury. DESIGN: TREM-2 expression was analysed in livers of humans with various forms of liver injury compared with control individuals...
January 27, 2018: Gut
Yen-Cheng Lin, Feng-Sheng Wang, Ya-Ling Yang, Yuan-Ting Chuang, Ying-Hsien Huang
Cholestasis and hepatitis can cause continuous liver damage that may ultimately result in liver fibrosis. In a previous study, we demonstrated that microRNA-29a (miR-29a) protects against liver fibrosis. Toll-like receptor 2 (TLR2) and TLR4 are pattern recognition receptors of bacterial lipoprotein and lipopolysaccharide, both of which participate in activating hepatic stellate cells and liver fibrosis. The purpose of this study is to characterize the biological influence of miR-29a on TLR2 and TLR4 signaling in livers injured with bile duct ligation (BDL)...
January 20, 2018: Biochemical and Biophysical Research Communications
Dan Liu, Yiyi Zhang, Yunhui Liu, Liqiong Hou, Sheyu Li, Haoming Tian, Tieyun Zhao
Berberine, a natural compound extracted from several Chinese herbs including Coptis chinensis, has been shown to have anti-obesity effects and prevents insulin resistance in high-fat diet (HFD)-fed obese rats by modulating the gut microbiota; however, the molecular mechanisms underlying these activities remain unknown. We investigated the effects of berberine on obesity and insulin resistance by examining the lipopolysaccharide (LPS)/toll-like receptor 4 (TLR4)/tumor necrosis factor (TNF)-α signaling pathway in livers of HFD-fed obese rats...
January 24, 2018: Experimental and Clinical Endocrinology & Diabetes
Xiaoli Chen, Xiuping Yan, Lu Guo
The present study investigated the inhibitory effect of Patrinia on lipopolysaccharide (LPS)-induced apoptosis of rat liver BRL‑3A cells. A Cell Counting Kit‑8 assay was performed to measure the effect of Patrinia on BLR‑3A cell activities. A biochemical assay was employed to detect the release of lactate dehydrogenase (LDH) in BRL‑3A cells induced by different doses of LPS. Based on the release rate of LDH, drug concentrations were set at 0.5, 1 and 2 g/l. Apoptotic morphology of cells was observed via Hoechst 33342 staining and flow cytometry was performed to detect apoptosis rates...
January 22, 2018: Molecular Medicine Reports
Kezhen Huang, Subhajit Mukherjee, Vera DesMarais, Joseph M Albanese, Ektor Rafti, Andrew Draghi, Leigh A Maher, Kamal M Khanna, Sridhar Mani, Adam P Matson
BACKGROUND: There is substantial evidence that signaling through Toll-like receptor 4 (TLR4) contributes to the pathogenesis of necrotizing enterocolitis (NEC). Pregnane X receptor (PXR), a xenobiotic sensor and signaling intermediate for certain host-bacterial metabolites, has been shown to negatively regulate TLR4 signaling. Here we investigated the relationship between PXR and TLR4 in the developing murine intestine and explored the capacity of PXR to modulate inflammatory pathways involved in experimental NEC...
January 23, 2018: Pediatric Research
Shoichi Kageyama, Kojiro Nakamura, Takehiro Fujii, Bibo Ke, Rebecca A Sosa, Elaine F Reed, Nakul Datta, Ali Zarrinpar, Ronald W Busuttil, Jerzy W Kupiec-Weglinski
Hepatic ischemia-reperfusion injury (IRI) represents a major risk factor of early graft dysfunction and acute/chronic rejection as well as a key obstacle to expanding the donor pool in orthotopic liver transplantation (OLT). Although glucocorticoid receptor (GR) signaling may enhance cytoprotective programs, clinical use of glucocorticoid is limited due to adverse effects, while clinical relevance of GR-facilitated cytoprotection in OLT remains unknown. We aimed to evaluate the significance of hepatic GR in clinical OLT and verify the impact of recombinant human relaxin (rhRLX), which may function as GR agonist in tissue/disease-specific manner...
January 19, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Jin Li, Bo Chen, Liping Zhong, Feng Gao, Haibo Zhu, Fengzhong Wang
Both AMP-activated protein kinase (AMPK) agonist and inhibitor have been reported to protect against fulminant hepatitis, implying that AMPK may play a complicated role in the development of fulminant hepatitis. In this study, we exploited whether the novel AMPK agonist N6-(3-hydroxyphenyl)adenosine (named as M1) exerted protective effects on fulminant hepatitis and whether its beneficial effects were AMPK-dependent. Results showed that intraperitoneal injection of M1 improved liver function, ameliorated liver injury and finally raised the survival rate in D-galactosamine/lipopolysaccharide (GalN/LPS)-treated mice...
January 18, 2018: Cell Death & Disease
Yuhan Chen, Zhifeng Wu, Baoying Yuan, Yinying Dong, Li Zhang, Zhaochong Zeng
Elevated toll-like receptor 4 (TLR4) expression is associated with a high risk of radiation-induced liver disease (RILD). MicroRNA (miR)-146a-5p is a key regulator of lipopolysaccharide (LPS)/TLR4 signaling, but its role in modulation of RILD remains unclear. Here, we found that irradiation and LPS stimulation induced TLR4 and miR-146a-5p expression in the human hepatic stellate cell (HSC) line LX2. Ectopic expression of miR-146a-5p in LX2 inhibited irradiation-induced and LPS-induced pro-inflammatory cytokine secretion and cell proliferation, and promoted cell apoptosis by down-regulating the expression levels of TLR4, interleukin-1 receptor associated kinase 1 (IRAK1), tumor necrosis factor receptor associated factor 6 (TRAF6) and phosphorylation of nuclear factor-kappa B...
January 18, 2018: Cell Death & Disease
Dariush Mozaffarian, Jason H Y Wu
A growing body of nutritional science highlights the complex mechanisms and pleiotropic pathways of cardiometabolic effects of different foods. Among these, some of the most exciting advances are occurring in the area of flavonoids, bioactive phytochemicals found in plant foods; and in the area of dairy, including milk, yogurt, and cheese. Many of the relevant ingredients and mechanistic pathways are now being clarified, shedding new light on both the ingredients and the pathways for how diet influences health and well-being...
January 19, 2018: Circulation Research
Jian Song, Xin Han, You-Li Yao, Ya-Mei Li, Jing Zhang, Dan-Yang Shao, Li-Shuang Hou, Ying Fan, Shun-Zong Song, Li-Hua Lian, Ji-Xing Nan, Yan-Ling Wu
OBJECTIVES: In alcoholic liver disease, alcohol and lipopolysaccharide (LPS) are major stimulation factors of hepatic lipogenesis. Our objective was to determine the protective mechanism of acanthoic acid (AA) in EtOH- and LPS-induced hepatic lipogenesis. METHODS: HSC-T6 cells were treated with ethanol (200 mm) plus LPS (1 μg/ml) for 1 h, followed by AA (10 or 20 μm) for another 6 h. C57BL/6 mice were pretreated with of AA (20 and 40 mg/kg) or equal volume of saline and then exposed to three doses of ethanol (5 g/kg body weight) within 24 h...
January 17, 2018: Journal of Pharmacy and Pharmacology
Xiang-Wen Gong, Yong-Jian Xu, Qin-He Yang, Yin-Ji Liang, Yu-Pei Zhang, Guan-Long Wang, Yuan-Yuan Li
OBJECTIVE: To investigate the mechanism of inflammatory-mediated toll-like receptor 4 (TLR4)-p38 mitogen-activated protein kinase (p38 MAPK) pathway in Kupffer cells (KCs) of non-alcoholic steatohepatitis (NASH) rats and the intervention effect of soothing Gan (Liver) and invigorating Pi (Spleen) recipes on this pathway. METHODS: After 1 week of acclimatization, 120 Sprague-Dawley male rats were randomly divided into 8 groups using a random number table (n=15 per group): normal group, model group, low-dose Chaihu Shugan Powder (, CHSG) group (3...
January 9, 2018: Chinese Journal of Integrative Medicine
Marijana Basic, Manuela Buettner, Lydia M Keubler, Anna Smoczek, Inga Bruesch, Stephanie Buchheister, André Bleich
The TLR4 co-receptor CD14 was identified as an IBD candidate gene. Here, its influence on the intestinal barrier was addressed utilizing E. coli Nissle (EcN), which induces severe inflammation in germfree TLR4-/- mice. After monoassociation, EcN was detected in spleens and livers of TLR4-/- and CD14-/- but not wildtype mice. Barrier impairment was characterized by increased apoptosis and decreased epithelial junction (EJ) expression and was reversed by TLR2 stimulation in CD14-/- mice. Bone marrow (BM) transplantation revealed contribution of hematopoietic and non-hematopoietic cells towards intestinal homeostasis...
January 15, 2018: Scientific Reports
Lorenzo A Orci, Stéphanie Lacotte, Vaihere Delaune, Florence Slits, Graziano Oldani, Vladimir Lazarevic, Carlo Rossetti, Laura Rubbia-Brandt, Philippe Morel, Christian Toso
BACKGROUND & AIMS: There is growing evidence that liver graft ischemia-reperfusion (I/R) is a risk factor for hepatocellular carcinoma (HCC) recurrence, but the involved mechanisms are unclear. Here, we tested the hypothesis that mesenteric congestion due to portal blood flow interruption induces endotoxin-mediated Toll-Like Receptor 4 (Tlr4) engagement, resulting in elevated liver cancer burden. We also assessed the role of remote ischemic preconditioning (RIPC) in this context. METHODS: C57Bl/6j mice were exposed to standardized models of liver I/R injury and RIPC, by occluding hepatic and femoral blood vessels...
January 10, 2018: Journal of Hepatology
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