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Tlr4 liver

Jarrod Sonett, Monica Goldklang, Piotr Sklepkiewicz, Adam Gerber, Jordis Trischler, Tina Zelonina, Marit Westerterp, Vincent Lemaître, Yasunori Okada, Jeanine D'Armiento
Macrophage infiltration is common to both emphysema and atherosclerosis, and cigarette smoke down-regulates the macrophage cholesterol efflux transporter ATP binding cassette (ABC)A1. This decreased cholesterol efflux results in lipid-laden macrophages. We hypothesize that cigarette smoke adversely affects cholesterol transport via an ABCA1-dependent mechanism in macrophages, enhancing TLR4/myeloid differentiation primary response gene 88 (Myd88) signaling and resulting in matrix metalloproteinase (MMP) up-regulation and exacerbation of pulmonary inflammation...
June 15, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Chenqing Ning, Xiaoguang Gao, Changyuan Wang, Xiaokui Huo, Zhihao Liu, Huijun Sun, Xiaobo Yang, Pengyuan Sun, Xiaodong Ma, Qiang Meng, Kexin Liu
Acute liver injury (ALI) is a dramatic liver disease characterized by large areas of inflammation in the liver. This study aimed to investigate the protective effects of ginsenoside Rg1 (Rg1), a biologically active component in Panax ginseng, on lipopolysaccharide/d-galactosamine (LPS/D-GalN)-induced ALI in mice, and meanwhile explore the molecular mechanism in vivo and in vitro. Mice were pretreated with Rg1 for three days prior to LPS (40 μg/kg)/D-GalN (700 mg/kg) administration. The results showed that Rg1 improved the survival rate and reduced the liver to body weight ratios in mice...
June 11, 2018: International Immunopharmacology
Biqiong Ren, Shudi Luo, Xuefei Tian, Zhichao Jiang, Guoying Zou, Fei Xu, Tieqiu Yin, Yiran Huang, Junlong Liu
Curcumin has been revealed to inhibit liver cancer, however, no studies have reported that the mechanism of curcumin's action on liver cancer is related to damage-associated molecular pattern (DAMP) molecules heat shock protein 70 (HSP70) and the toll-like receptor 4 (TLR4) signaling. This study aimed to investigate whether the activation of TLR4 signaling by HSP70 could be inhibited by curcumin, thus investigating the possible mechanism of curcumin in the inhibition of liver cancer. Western blotting was used to evaluate the expression of the HSP70 and TLR4 in HepG2 cells and ELISA was used to detect the concentration of HSP70 in cell culture medium...
June 11, 2018: Oncology Reports
Zhixiang Xie, Zhuangbo Guo, Jianfeng Liu
BACKGROUND Whey acidic protein/four-disulfide core domain 21 (Wfdc21), also known as Lnc-DC, it has been reported to be correlated with immune response. However, the role of Wfdc21 in the pathogenesis of sepsis is still unknown. In the present study, we aimed to investigate the role of Wfdc21 in the pathogenesis of sepsis. MATERIAL AND METHODS The cecal ligation and puncture (CLP)-induced sepsis model was established in Balb/c mice. Animals were euthanized 4, 8, 16, or 24 h after CLP. The glycogen distribution in the kidney and liver was checked by Periodic acid-Schiff (PAS) staining...
June 14, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Ping Ya, Henggui Xu, Yanmin Ma, Mengxiong Fang, Xiaomei Yan, Jie Zhou, Fasheng Li
Accumulating evidence has suggested a strong link between exposure to air pollution and public health. In particular, inhaled airborne particulate matter <2.5 μm in aerodynamic diameter (PM2.5 ) can rapidly diffuse from the lungs to the systemic blood circulation and accumulate in the liver. In this study, we used a Balb/c mouse model to investigate liver injury caused by PM2.5 inhalation and the anti-inflammatory and antioxidant effects of compound essential oils (CEOs) in alleviating the extent of this injury...
June 8, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Lin Jia, Xiuli Chang, Shuwen Qian, Chen Liu, Caleb C Lord, Newaz Ahmed, Charlotte E Lee, Syann Lee, Laurent Gautron, Mack C Mitchell, Jay D Horton, Philipp E Scherer, Joel K Elmquist
OBJECTIVE: Recent studies have suggested a critical role for toll-like receptor 4 (TLR4) in the development of alcoholic liver disease. As TLR4 is widely expressed throughout the body, it is unclear which TLR4-expressing cell types contribute to alcohol-induced liver damage. METHODS: We selectively ablated TLR4 in hepatocytes and myeloid cells. Male mice were fed a liquid diet containing either 5% alcohol or pair-fed a control diet for 4 weeks to examine chronic alcohol intake-induced liver damage and inflammation...
May 23, 2018: Molecular Metabolism
Yuan-Hsi Wang, Yuh-Ching Twu, Chung-Kwe Wang, Fu-Zhen Lin, Chun-Ya Lee, Yi-Jen Liao
Liver fibrosis is the first step toward the progression to cirrhosis, portal hypertension, and hepatocellular carcinoma. A high-cholesterol diet is associated with liver fibrosis via the accumulation of free cholesterol in hepatic stellate cells (HSCs). Niemann-Pick type C2 (NPC2) plays an important role in the regulation of intracellular free cholesterol homeostasis via direct binding with free cholesterol. Previously, we reported that NPC2 was downregulated in liver cirrhosis tissues. Loss of NPC2 enhanced the accumulation of free cholesterol in HSCs and made them more susceptible to transforming growth factor (TGF)-β1...
June 5, 2018: International Journal of Molecular Sciences
Ke-Ke Jia, Shu-Man Pan, Hong Ding, Jia-Hui Liu, Yan-Jing Zheng, Shui-Juan Wang, Ying Pan, Ling-Dong Kong
Depression is a mental illness comorbid risk factor for glucose intolerance worldwide. Chaihu-shugan san, a 'Shu-Gan' formula in traditional Chinese medicine, is clinically used in the treatment of depression. The aim of this study was to investigate whether Chaihu-shugan san improved glucose tolerance with its antidepressant activity in rat model of depression and explore the mechanisms underlying its action on liver-brain inflammation axis. After 6 weeks of chronic unpredictable mild stress (CUMS) procedure, male Wistar rats were given Chaihu-shugan san water extract (925 and 1850 mg/kg) by gavage for the next 6 consecutive weeks...
July 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Shan-Shan Li, Min Yang, Yong-Ping Chen, Xin-Yue Tang, Sheng-Guo Zhang, Shun-Lan Ni, Nai-Bin Yang, Ming-Qin Lu
Acute liver failure is a devastating clinical syndrome with extremely terrible inflammation reaction, which is still lack of effective treatment in clinic. Suppressor of Cytokine Signaling 1 protein is inducible intracellular negative regulator of Janus kinases (JAK)/signal transducers and activators of transcription (STAT) pathway that plays essential role in inhibiting excessive intracellular signaling cascade and preventing autoimmune reaction. In this paper, we want to explore whether dendritic cells (DCs) with overexpression of SOCS1 have a therapeutic effect on experimental acute liver failure...
May 28, 2018: Molecular Immunology
Johannes Maximilian Ludwig, Yuling Zhang, Walee Chamulitrat, Wolfgang Stremmel, Anita Pathil
AIM: Endotoxin-mediated liver inflammation is a key component of many acute and chronic liver diseases contributing to liver damage, fibrosis and eventually organ failure. Here, we investigated ursodeoxycholyl lysophosphatidylethanolamide (UDCA-LPE), a synthetic bile acid-phospholipid conjugate regarding its anti-inflammatory and anti-fibrogenic properties. METHODS: Anti-inflammatory properties of UDCA-LPE were evaluated in a mouse model of D-galactosamine/lipopolysaccharide (GalN/LPS)-induced acute liver injury, LPS treated RAW264...
2018: PloS One
Gang Chi, Xin-Xia Feng, Ying-Xia Ru, Ting Xiong, Yuan Gao, Han Wang, Zhen-Long Luo, Ran Mo, Fang Guo, Yong-Pei He, Gui-Mei Zhang, De-An Tian, Zuo-Hua Feng
Autoimmune hepatitis (AIH), a serious autoimmune liver disease, can be a lifelong illness, leading to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). So far the mechanisms for disease initiation are largely unknown. Here we report that the amplified non-AIH liver inflammation could promote the initiation of AIH due to the sustained increase of IL-6, IL-12, IL-4, and IL-25 in the liver. The liver injury resulting from virus (adenovirus) or chemicals (CCl4 ) could induce an amplified (stronger/long-lasting) hepatic inflammation by releasing the ligands for TLR2/TLR4...
July 2018: Molecular Immunology
Qinlong Liu, Hasibur Rehman, Yasodha Krishnasamy, John J Lemasters, Zhi Zhong
Pulmonary complications frequently occur after liver transplantation and are often life-threatening. Thus, we investigated whether hepatic ischemic preconditioning (IP) attenuates acute lung injury (ALI) after small-for-size liver transplantation. Rat livers were explanted after 9-min ischemia plus 5-min reperfusion, reduced to 50% of original size ex vivo , and implanted into recipients with approximately twice the donor body weight, resulting in quarter-size liver grafts (QSG). After QSG transplantation, hepatic Toll-like receptor 4 (TLR4) and tumor necrosis factor-α (TNFα ) expression increased markedly and high mobility group box-1 (HMGB1), an endogenous damage-associated molecular pattern molecule (DAMP), was released from QSG into the blood...
2018: International Journal of Physiology, Pathophysiology and Pharmacology
Ratanesh Kumar Seth, Diana Kimono, Firas Alhasson, Sutapa Sarkar, Muayad Albadrani, Stephen K Lasley, Ronnie Horner, Patricia Janulecewicz, Mitzi Nagarkatti, Prakash Nagarkatti, Kimberly Sullivan, Saurabh Chatterjee
Most of the associated pathologies in Gulf War Illness (GWI) have been ascribed to chemical and pharmaceutical exposures during the war. Since an increased number of veterans complain of gastrointestinal (GI), neuroinflammatory and metabolic complications as they age and there are limited options for a cure, the present study was focused to assess the role of butyrate, a short chain fatty acid for attenuating GWI-associated GI and metabolic complications. Results in a GWI-mouse model of permethrin and pyridostigmine bromide (PB) exposure showed that oral butyrate restored gut homeostasis and increased GPR109A receptor copies in the small intestine (SI)...
May 8, 2018: Toxicology and Applied Pharmacology
Liteng Lin, Rui Li, Mingyue Cai, Jingjun Huang, Wensou Huang, Yongjian Guo, Liuhong Yang, Guizhi Yang, Tian Lan, Kangshun Zhu
Liver fibrosis is characterized by activated hepatic stellate cells (HSC) and extracellular matrix accumulation. Blocking the activation of HSC and the inflammation response are two major effective therapeutic strategies for liver fibrosis. In addition to the long history of using andrographolide (Andro) for inflammatory disorders, we aimed at elucidating the pharmacological effects and potential mechanism of Andro on liver fibrosis. In this study, liver fibrosis was induced by carbon tetrachloride (CCl4 ) and the mice were intraperitoneally injected with Andro for 6 weeks...
2018: Oxidative Medicine and Cellular Longevity
Jianjun Xu, Caijiao Lu, Zhengjun Liu, Peng Zhang, Hailei Guo, Tingting Wang
Schizandrin B ( Sch B ) is the main component isolated from Schizandra fruit ( Schisandra chinensis ). While Sch B is established as having antioxidant, anti-proliferation and anti-inflammatory properties, but its activity in sepsis remains unclear. In the present study, we investigated the anti-inflammatory effects of Sch B in sepsis. Our experimental results demonstrated that Sch B inhibited production of IL-1β, TNF-α, IL-6 and HMGB1 by LPS-activated RAW264.7 cells. Moreover, Sch B suppressed expression of iNOS, reduced production of PGE2, blocked expression of MyD88 and TLR4, suppressed the activity of NF-κB and decreased phosphorylation of MAPKs in LPS-activated RAW264...
2018: American Journal of Translational Research
Yao Wang, Hui Chen, Qian Chen, Fang-Zhou Jiao, Wen-Bin Zhang, Zuo-Jiong Gong
The purpose of this study was to investigate the protective mechanism of HDAC2 inhibitor CAY10683 on intestinal mucosal barrier in acute liver failure (ALF). In order to establish ALF-induced intestinal epithelial barrier disruption models, D-galactosamine/LPS and LPS were, respectively, used with rats and NCM460 cell and then administrated with CAY10683. Transepithelial electrical resistance (TEER) was measured to detect the permeability of cells. Real-time PCR and Western blotting were employed to detect the key mRNA and protein levels...
2018: Mediators of Inflammation
Yupei Zhang, Kairui Tang, Yuanjun Deng, Runsen Chen, Shu Liang, Huijun Xie, Yifang He, Yanning Chen, Qinhe Yang
BACKGROUND: Worldwide, non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease closely associated with obesity, diabetes and other metabolic diseases. Shenling Baizhu powder (SLBZP), a formulation of a variety of natural medicinal plants, has hepatoprotective properties and clinical efficacy in treating non-infectious intestinal disease. SLBZP has improved NAFLD symptoms; however, its mechanism of action is unknown. METHODS: We established an NAFLD model in rats given a high-fat diet (HFD), administered different interventions and measured serum biochemical indices and inflammatory factors...
June 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Yong Zhang, Xiaoming Lei, Wei Li, Xiaoying Ding, Jie Bai, Jin Wang, Gang Wu
Hepatic ischemia/reperfusion (I/R) injury induces oxidative stress, hepatocyte apoptosis, and release of inflammatory cytokines, which together causes liver damage and even organ dysfunction. TNF-α-induced protein 3-interacting protein 1 (TNIP1) reportedly decreases expression of genes associated with stress response and inflammation. Thus, we investigated the effects of TNIP1 on hepatic cells injury caused by hypoxia/reoxygenation (H/R). Reduced expression of TNIP1 was determined in I/R mice compared to normal mice...
June 18, 2018: Biochemical and Biophysical Research Communications
Benjamin Wolfson, Pang-Kuo Lo, Yuan Yao, Linhao Li, Hongbing Wang, Qun Zhou
SCOPE: We have previously shown that loss of miR-140 has a pro-fibrotic effect in the mammary gland. This study aims to investigate whether miR-140 loss and obesity act synergistically to promote non-alcoholic fatty liver disease (NAFLD), and to identify the underlying mechanisms. METHODS AND RESULTS: Liver tissues were isolated from lean-fat-diet and high-fat-diet fed wild-type and miR-140 knockout mice. Using molecular staining and immunohistochemistry techniques, increased development of NAFLD and fibrotic indicators in miR-140 knockout mice were identified...
April 27, 2018: Molecular Nutrition & Food Research
Xue-Tao Yan, Xiang-Hu He, Yan-Lin Wang, Zong-Ze Zhang, Jun-Jiao Tang
Oxidative stress and inflammation have been identified to play a vital role in the pathogenesis of lung injury induced by septic shock. Heme oxygenase-1 (HO-1), an effective antioxidant and anti-inflammatory and antiapoptotic substance, has been used for the treatment of heart, lung, and liver diseases. Thus, we postulated that administration of exogenous HO-1 protein transduced by cell-penetrating peptide PEP-1 has a protective role against septic shock-induced lung injury. Septic shock produced by cecal ligation and puncture caused severe lung damage, manifested in the increase in the lung wet/dry ratio, oxidative stress, inflammation, and apoptosis...
2018: Oxidative Medicine and Cellular Longevity
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