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Kupffer cell

Salvatore Sutti, Frank Tacke
Drug-induced liver injury (DILI) remains a clinical challenge due to the poorly predictable outcomes. Accordingly, considerable efforts have been devoted to unravel the risk factors responsible for DILI worsening toward acute liver failure (ALF), liver transplantation (LT), and/or death. From a pathogenic point of view, exhaustion of drug metabolizing pathways, cell death mechanisms, activation of local immune cells, such as Kupffer cells, and recruitment of inflammatory leukocytes including monocytes and lymphocytes are key drivers of DILI progression...
March 15, 2018: Clinical Science (1979-)
Vahid Mirshafiee, Bingbing Sun, Chong Hyun Chang, Yu-Pei Liao, Wen Jiang, Jinhong Jiang, Xiangsheng Liu, Xiang Wang, Tian Xia, Andre E Nel
The liver and the mononuclear phagocyte system (MPS) is a frequent target for engineered nanomaterials (ENMs), either as a result of particle uptake and spread from primary exposure sites or systemic administration of therapeutic and imaging nanoparticles. In this study, we performed a comparative analysis of the toxicological impact of 29 metal oxide (MOx) nanoparticles (NPs), some commonly used in consumer products, in transformed or primary Kupffer cells (KCs) and hepatocytes. Not only did we observe differences between KC and hepatocytes, but also differences in the toxicological profiles of transition metal oxides (TMOs, e...
March 15, 2018: ACS Nano
Sam J L van der Tuin, Zhuang Li, Jimmy F P Berbée, Inge Verkouter, Linda E Ringnalda, Annette E Neele, Jan B van Klinken, Sander S Rensen, Jingyuan Fu, Menno P J de Winther, Albert K Groen, Patrick C N Rensen, Ko Willems van Dijk, Yanan Wang
BACKGROUND: Lipopolysaccharide (LPS) decreases hepatic CETP (cholesteryl ester transfer protein) expression albeit that the underlying mechanism is disputed. We recently showed that plasma CETP is mainly derived from Kupffer cells (KCs). In this study, we investigated the role of KC subsets in the mechanism by which LPS reduces CETP expression. METHODS AND RESULTS: In CETP-transgenic mice, LPS markedly decreased hepatic CETP expression and plasma CETP concentration without affecting hepatic macrophage number...
March 10, 2018: Journal of the American Heart Association
Valentina Caracciolo, Jeanette Young, Donna Gonzales, Yinchun Ni, Stephen J Flowers, Ross Summer, Scott A Waldman, Jason K Kim, Dae Young Jung, Hye Lim Noh, Taekyoon Kim, Perry J Blackshear, Danielle O'Connell, Robert C Bauer, Caleb B Kallen
Obesity is associated with adipose tissue inflammation that contributes to insulin resistance. Zinc Finger Protein 36 (Zfp36) is an mRNA-binding protein that reduces inflammation by binding to cytokine transcripts and promoting their degradation. We hypothesized that myeloid-specific deficiency of Zfp36 would lead to increased adipose tissue inflammation and reduced insulin sensitivity in diet-induced obese mice. As expected, wild type (Control) mice became obese and diabetic on a high-fat diet and obese mice with myeloid-specific loss of Zfp36 (KO) demonstrated increased adipose tissue and liver cytokine mRNA expression compared to Control mice...
March 6, 2018: American Journal of Physiology. Endocrinology and Metabolism
Shigeyuki Takamatsu, Kazuto Kozaka, Satoshi Kobayashi, Norihide Yoneda, Kotaro Yoshida, Dai Inoue, Azusa Kitao, Takahiro Ogi, Tetsuya Minami, Wataru Kouda, Tomoyasu Kumano, Nobukazu Fuwa, Osamu Matsui, Toshifumi Gabata
Recent advances in highly conformal radiotherapies greatly extend the indications for radiotherapy of liver tumors. However, because of poor tolerance to hepatic radiation, estimation of the intensity of irradiation of the liver is important, particularly for a cirrhotic liver. Knowledge of radiation-induced hepatitis is important for understanding how to optimize hepatic radiation therapy. Pathological changes of the irradiated liver, which include perivenular fibrosis, sinusoidal obstruction, and damage to Kupffer cells and hepatocytes, can be visualized using clinical imaging techniques...
March 5, 2018: Japanese Journal of Radiology
Rui Han, Fang Zhang, Chong Wan, Limin Liu, Qiang Zhong, Wenjun Ding
Perfluorooctane sulfonate (PFOS), one member of polyfluoroalkyl chemicals (PFASs), persist in the environment and are found in relatively high concentrations in animal livers. PFOS has been shown to induce tumour of the liver in rats following chronic dietary administration. However, the molecular mechanisms involved in PFOS-induced hepatocellular hypertrophy are still not well characterized. In this study, male Sprague-Dawley rats were daily gavaged with PFOS (1 or 10 mg/kg body weight) for 28 days. Rat primary cultured Kupffer cells or hepatocytes were exposed to 100 μM PFOS for 0-48 h...
February 23, 2018: Chemosphere
Rongtao Zhu, Weizhi Guo, Hongbo Fang, Shengli Cao, Bing Yan, Sanyang Chen, Kaiming Zhang, Shuijun Zhang
Brain death (BD) impairs liver function in potential donors, and is associated with hormonal and metabolic changes or molecular effects with pro‑inflammatory activation. Resident macrophages in the liver named Kupffer cells (KCs) undergo pro‑ or anti‑inflammatory pathway activation, which affects liver function. However, the role of the KCs in liver dysfunction following BD has not been fully elucidated. The aim of the present study was to investigate the role of KCs in liver dysfunction in the context of BD and the effects of their inhibition by gadolinium chloride (GdCl3)...
February 27, 2018: Molecular Medicine Reports
Mikako Warren, Gary Mierau, Eric P Wartchow, Hiroyuki Shimada, Shoji Yano
Zellweger spectrum disorders (ZSD) are rare autosomal recessive inherited metabolic disorders and include severe (Zellweger syndrome) and milder phenotypes [neonatal adrenoleukodystrophy and infantile Refsum disease (IRD)]. ZSD are characterized by impaired peroxisomal functions and lack of peroxisomes detected by electron microscopy (EM). ZSD are caused by mutations in any of the 14 PEX genes. Patients with ZSD commonly demonstrate nonspecific hepatic symptoms within the first year, often without clinical suspicion of ZSD...
February 26, 2018: Ultrastructural Pathology
Xiao-Qin Liu, Rong-Rong Wei, Cheng-Cheng Wang, Li-Yu Chen, Cong Liu, Kai Liu
Background/aim: This study aimed to investigate the potential regulatory role of prokineticin 2 (PK2) in modulation of the number and function of Kupffer cells (KCs) during the progression of liver fibrosis in patients with hepatitis B virus (HBV). Materials and methods: We obtained liver tissue sections from 200 patients with HBV undergoing surgical resection in our hospital between January 2013 and July 2016. Of these 200 tissue sections, 150 were fibrosis tissues and 50 were hepatocellular carcinoma tissues...
February 23, 2018: Turkish Journal of Medical Sciences
Li Su, Na Li, Hua Tang, Ziyang Lou, Xiaodan Chong, Chenxi Zhang, Jiacan Su, Xin Dong
The damage-associated molecular pattern molecules (DAMPs) released by necrotic cells can trigger inflammatory response, which will facilitate the clearance of these dead cells. Neutrophil mobilization is a very important step for the dead cell clearance, however the detailed mechanisms for DAMPs induce neutrophil mobilization remains largely elusive. In this study, by using a necrotic cell-induced neutrophil mobilization mice model, we found that both neutrophil number and percentage rapidly (as early as 30 min) increased with necrotic cells but not live cell treatment...
February 23, 2018: Cell Death & Disease
William Alazawi, Percy A Knolle
No abstract text is available yet for this article.
February 17, 2018: Journal of Hepatology
Luca Meoli, Nitin K Gupta, Nima Saeidi, Courtney Panciotti, Sudha B Biddinger, Kathleen E Corey, Nicholas Stylopoulos
Treatment of non-alcoholic fatty liver disease (NAFLD) focuses on the underlying metabolic syndrome, and Roux-en-Y gastric bypass surgery (RYGB) remains one of the most effective options. In rodents and human patients, RYGB induces an increase in the gene and protein expression levels of the M2 isoenzyme of Pyruvate Kinase (PKM2) in the jejunum. Since PKM2 can be secreted in the circulation, our hypothesis was that the circulating levels of PKM2 increase after RYGB. Our data, however, revealed an unexpected finding and a potential new role of PKM2 for the natural history of metabolic syndrome and NAFLD...
February 20, 2018: American Journal of Physiology. Endocrinology and Metabolism
Jia Liu, Qing Yu, Weimin Wu, Xuan Huang, Ruth Broering, Melanie Werner, Michael Roggendorf, Dongliang Yang, Mengji Lu
Hepatic APCs play a critical role in promoting immune tolerance in the liver. Recently, we have demonstrated that TLR2 stimulation on liver sinusoidal endothelial cells reverted their suppressive properties to induce T cell immunity. However, there is a paucity of information about how TLR2 stimulation modulates the immunological function of other hepatic APCs. In the current study, we investigated whether TLR2 stimulation influences the function of intrahepatic myeloid-derived cells (iMDCs) and elucidated the mechanisms involved in iMDC-induced T cell immunity...
February 19, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Mei Shigematsu, Shozo Tomonaga, Fumie Shimokawa, Masaru Murakami, Toru Imamura, Tohru Matsui, Masayuki Funaba
The liver is the organ that responds to nutritional disturbances including magnesium deficiency. The present study evaluated cellular responses to magnesium deficiency using model cells of the liver, namely, HepG2 cells as hepatocytes, RAW264.7 cells as Kupffer cells and human umbilical vein endothelial cells (HUVECs) as vascular endothelial cells; we examined effects of culture with magnesium deficient medium on cell responses in individual types of cells as well as interactive responses among cells. Metabolomic analyses indicated that magnesium deficiency differentially affected the cellular content of metabolites among HepG2 cells, RAW264...
February 2, 2018: Journal of Nutritional Biochemistry
Thomas Ritz, Oliver Krenkel, Frank Tacke
Liver macrophages attract increasing interest due to their crucial roles in homeostasis and hepatic diseases. Recent findings in mice and man suggest a remarkable phenotypic and functional diversity of liver macrophages. Kupffer cells, the subset of tissue resident macrophages with sentinel functions in liver, mainly arise from embryogenic precursors, whereas in injury, liver tissue is engrafted by monocyte-derived macrophages. Both principal macrophage populations respond to local or systemic signals and have substantial effects on reduction as well as aggravation of hepatic diseases...
December 20, 2017: Cellular Immunology
Mengyang Li, Xiaofeng Lai, Ying Zhao, Yuan Zhang, Minghui Li, Danxiu Li, Jing Kong, Yong Zhang, Pengyu Jing, Huichen Li, Hongyan Qin, Liangliang Shen, Libo Yao, Jipeng Li, Kefeng Dou, Jian Zhang
The liver is the predominant metastatic site for several types of malignancies. Tumor-associated macrophages (TAMs) in the liver play crucial roles in the metastasis process. Shifting tumor-promoting M2-like TAMs toward the M1-like phenotype, which exerts tumor suppressor functions via phagocytosis and the secretion of inhibitory factors, may be a potential therapeutic strategy for liver cancer metastasis treatment.We first cloned NDRG2 (N-myc downstream-regulated gene 2) and verified its tumor suppressor role in multiple solid tumors, including colorectal cancer and hepatocellular carcinoma...
February 14, 2018: Cell Death & Disease
Yingli Xie, Di Zhao, Pingshuan Dong, Lihong Lai
Macrophages play essential roles in the generation and resolution of inflammation. Ischemia-reperfusion injury (IRI) triggers a systemic inflammatory response and leads to cellular injury and organ failure. During surgical procedures of the liver, such as hepatic resection and liver transplantation, IRI leads to the dysfunction of the liver. Rho-associated protein kinase (ROCK) inhibitors were reported protecting the liver from IRI. However, the systematic administration of ROCK inhibitors causes severe hypotension...
February 12, 2018: Bioscience Reports
Wei Ying, Sumana Mahata, Gautam K Bandyopadhyay, Zhenqi Zhou, Joshua Wollam, Jessica Vu, Rafael Mayoral, Nai-Wen Chi, Nicholas J G Webster, Angelo Corti, Sushil K Mahata
The activation of Kupffer cells (KCs) and monocyte (Mc)-derived recruited macrophages (McMΦs) in the liver contributes to obesity-induced insulin resistance and type 2 diabetes. Diet-induced obese (DIO) mice treated with Chromogranin A (CgA) peptide catestatin (CST) showed several positive results. These included decreased hepatic/plasma lipids and plasma insulin, diminished expression of gluconeogenic genes, attenuated expression of pro-inflammatory genes, increased expression of anti-inflammatory genes in McMΦs, and inhibition of the infiltration of McMΦs resulting in improvement of insulin sensitivity...
February 6, 2018: Diabetes
Scott P Davies, Gary M Reynolds, Zania Stamataki
Toxic substances and microbial or food-derived antigens continuously challenge the liver, which is tasked with their safe neutralization. This vital organ is also important for the removal of apoptotic immune cells during inflammation and has been previously described as a "graveyard" for dying lymphocytes. The clearance of apoptotic and necrotic cells is known as efferocytosis and is a critical liver function to maintain tissue homeostasis. Much of the research into this form of immunological control has focused on Kupffer cells, the liver-resident macrophages...
2018: Frontiers in Immunology
Chih-Sung Hsieh, Jiin-Haur Chuang, Ming-Huei Chou, Ying-Hsien Kao
The role of transforming growth factor-β activated kinase 1 (TAK1) in modulating the function of Kupffer cells (KCs) within cholestatic livers remains unclear. This study examined the immunopharmacological action of dexamethasone (DEX) in modulating hepatic TAK1 expression and related signaling activity in a rat model of bile duct ligation-mimicked obstructive jaundice. The in vitro effects of DEX on porcine biliary extract (PBE)-modulated gene expression and phagocytosis of KCs were examined using a rat alveolar macrophage cell line (NR8383 cells)...
February 4, 2018: International Immunopharmacology
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