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Macrophage metabolism

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https://www.readbyqxmd.com/read/27923151/a-novel-role-for-the-kr%C3%A3-ppel-like-factor-14-on-macrophage-inflammatory-response-and-atherosclerosis-development
#1
Xiao Wei, Ruomei Yang, Chengpan Wang, Xun Jian, Ling Li, Hua Liu, Gangyi Yang, Zhiyong Li
Genome-wide association studies have shown that Krüppel-like factor 14 (KLF14) is associated with both Type 2 diabetes mellitus and lipid metabolism. However, its role in chronic inflammatory responses and the pathogenesis of atherosclerosis remains unknown. The present study was designed to investigate both in vivo and in vitro the impact of KLF14 on chronic inflammatory responses and atherosclerosis. ApoE KO mice, a well-established animal model of atherosclerosis, had higher expressions of KLF14 in aorta tissues than that in C57BL/6 J mice when fed the high-fat diet (HFD) or standard chow diet...
November 14, 2016: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
https://www.readbyqxmd.com/read/27920274/adipose-fatty-acid-binding-protein-promotes-saturated-fatty-acid-induced-macrophage-cell-death-through-enhancing-ceramide-production
#2
Yuwen Zhang, Enyu Rao, Jun Zeng, Jiaqing Hao, Yanwen Sun, Shujun Liu, Edward R Sauter, David A Bernlohr, Margot P Cleary, Jill Suttles, Bing Li
Macrophages play a critical role in obesity-associated chronic inflammation and disorders. However, the molecular mechanisms underlying the response of macrophages to elevated fatty acids (FAs) and their contribution to metabolic inflammation in obesity remain to be fully elucidated. In this article, we report a new mechanism by which dietary FAs, in particular, saturated FAs (sFAs), are able to directly trigger macrophage cell death. We demonstrated that excess sFAs, but not unsaturated FAs, induced the production of cytotoxic ceramides (Cers) in macrophage cell lines...
December 5, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27918207/gemigliptin-ameliorates-western-diet-induced-metabolic-syndrome-in-mice
#3
Seung Hee Choi, Jaechan Leem, Sungmi Park, Chong-Kee Lee, Keun-Gyu Park, In-Kyu Lee
Dipeptidyl peptidase 4 (DPP-4) inhibitors are widely used antihyperglycemic agents for type 2 diabetes mellitus. Recently, increasing attention has been focused on the pleiotropic actions of DPP-4 inhibitors. The aim of the present study was to examine whether gemigliptin, a recently developed DPP-4 inhibitor, could ameliorate features of metabolic syndrome. Mice were fed a Western diet (WD) for 12 weeks and were subsequently divided into 2 groups: mice fed a WD diet alone or mice fed a WD diet supplemented with gemigliptin for an additional 4 weeks...
September 4, 2016: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/27916296/ampk%C3%AE-is-suppressed-in-bladder-cancer-through-macrophage-mediated-mechanisms
#4
Stavros Kopsiaftis, Poornima Hegde, John A Taylor, Kevin P Claffey
Bladder cancer presents as either low- or high-grade disease, each with distinct mutational profiles; however, both display prominent mTORC1 activation. One major negative regulator of mTORC1 is AMPK, which is a critical metabolic regulator that suppresses cellular growth in response to metabolic stress by negatively regulating mTORC1. Alterations in the activation and protein levels of AMPK have been reported in breast, gastric, and hepatocellular carcinoma. To investigate whether AMPK suppression is responsible for mTOR activation in bladder cancer, the levels of AMPKα were quantified in a cohort of primary human bladder cancers and adjacent nontumor tissues...
December 2016: Translational Oncology
https://www.readbyqxmd.com/read/27914363/new-insights-into-the-sar-and-drug-combination-synergy-of-2-quinolin-4-yloxy-acetamides-against-mycobacterium-tuberculosis
#5
Bruno Couto Giacobbo, Kenia Pissinate, Valnês Rodrigues-Junior, Anne Drumond Villela, Estêvão Silveira Grams, Bruno Lopes Abbadi, Fernanda Teixeira Subtil, Nathalia Sperotto, Rogério Valim Trindade, Davi Fernando Back, Maria Martha Campos, Luiz Augusto Basso, Pablo Machado, Diógenes Santiago Santos
2-(Quinolin-4-yloxy)acetamides have been described as potent and selective in vitro inhibitors of Mycobacterium tuberculosis (Mtb) growth. Herein, a new series of optimized compounds were found to demonstrate highly potent antitubercular activity, with minimum inhibitory concentration (MIC) values against drug-susceptible and drug-resistant Mycobacterium tuberculosis strains in the submicromolar range. Furthermore, the most active compounds had no apparent toxicity to mammalian cells, and they showed intracellular activities similar to those of isoniazid and rifampin in a macrophage model of Mtb infection...
November 23, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27914007/evaluation-of-68-ga-labeled-peptide-tracer-for-detection-of-gelatinase-expression-after-myocardial-infarction-in-rat
#6
Max Kiugel, Ville Kytö, Tiina Saanijoki, Heidi Liljenbäck, Olli Metsälä, Mia Ståhle, Johanna Tuomela, Xiang-Guo Li, Pekka Saukko, Juhani Knuuti, Anne Roivainen, Antti Saraste
BACKGROUND: Matrix metalloproteinases 2 and 9 (MMP-2/9) play a role in extracellular matrix remodeling after an ischemic myocardial injury. We evaluated (68)Ga-DOTA-peptide targeting MMP-2/9 for the detection of gelatinase expression after myocardial infarction (MI) in rat. METHODS: Rats were injected with 43 ± 7.7 MBq of (68)Ga-DOTA-peptide targeting MMP-2/9 at 7 days (n = 7) or 4 weeks (n = 8) after permanent coronary ligation or sham operation (n = 5 at both time points) followed by positron emission tomography (PET)...
December 2, 2016: Journal of Nuclear Cardiology: Official Publication of the American Society of Nuclear Cardiology
https://www.readbyqxmd.com/read/27910911/human-mesenchymal-stem-cells-program-macrophage-plasticity-by-altering-their-metabolic-status-via-a-pge2-dependent-mechanism
#7
Anoop Babu Vasandan, Sowmya Jahnavi, Chandanala Shashank, Priya Prasad, Anujith Kumar, S Jyothi Prasanna
Mesenchymal stem cells (MSCs) are speculated to act at macrophage-injury interfaces to mediate efficient repair. To explore this facet in-depth this study evaluates the influence of MSCs on human macrophages existing in distinct functional states. MSCs promoted macrophage differentiation, enhanced respiratory burst and potentiated microbicidal responses in naïve macrophages (Mφ). Functional attenuation of inflammatory M1 macrophages was associated with a concomitant shift towards alternatively activated M2 state in MSC-M1 co-cultures...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27909560/induction-of-heme-oxygenase-1-with-dietary-quercetin-reduces-obesity-induced-hepatic-inflammation-through-macrophage-phenotype-switching
#8
Chu-Sook Kim, Hye-Seon Choi, Yeonsoo Joe, Hun Taeg Chung, Rina Yu
BACKGROUND/OBJECTIVES: Obesity-induced steatohepatitis accompanied by activated hepatic macrophages/Kupffer cells facilitates the progression of hepatic fibrinogenesis and exacerbates metabolic derangements such as insulin resistance. Heme oxyganase-1 (HO-1) modulates tissue macrophage phenotypes and thus is implicated in protection against inflammatory diseases. Here, we show that the flavonoid quercetin reduces obesity-induced hepatic inflammation by inducing HO-1, which promotes hepatic macrophage polarization in favor of the M2 phenotype...
December 2016: Nutrition Research and Practice
https://www.readbyqxmd.com/read/27908890/pathology-of-human-coronary-and-carotid-artery-atherosclerosis-and-vascular-calcification-in-diabetes-mellitus
#9
Kazuyuki Yahagi, Frank D Kolodgie, Christoph Lutter, Hiroyoshi Mori, Maria E Romero, Aloke V Finn, Renu Virmani
The continuing increase in the prevalence of diabetes mellitus in the general population is predicted to result in a higher incidence of cardiovascular disease. Although the mechanisms of diabetes mellitus-associated progression of atherosclerosis are not fully understood, at clinical and pathological levels, there is an appreciation of increased disease burden and higher levels of arterial calcification in these subjects. Plaques within the coronary arteries of patients with diabetes mellitus generally exhibit larger necrotic cores and significantly greater inflammation consisting mainly of macrophages and T lymphocytes relative to patients without diabetes mellitus...
December 1, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27905947/fibroblast-growth-factor-21-potentially-inhibits-microrna-33-expression-to-affect-macrophage-actions
#10
EDITORIAL
Yuan Guo, Fei Luo, Yuhong Yi, Danyan Xu
Atherosclerosis is a chronic inflammatory disease with complex pathological processes. MicroRNA-33 (miR-33), a novel non-coding RNA that coexpresses with sterol regulatory element-binding proteins (SREBPs), affects macrophage actions to prevent atherosclerosis. Fibroblast growth factor 21 (FGF21) is an important regulator of lipid metabolism, especially for macrophage-related cholesterol export, but the mechanism is not fully studied. Interestingly, FGF21 has been evidenced to prevent atherosclerosis via inhibiting SREBP-2 expression...
December 1, 2016: Lipids in Health and Disease
https://www.readbyqxmd.com/read/27903745/inhibiting-microglia-expansion-prevents-diet-induced-hypothalamic-and-peripheral-inflammation
#11
Caroline André, Omar Guzman-Quevedo, Charlotte Rey, Julie Rémus-Borel, Samantha Clark, Ashley Castellanos-Jankiewicz, Elodie Ladeveze, Thierry Leste-Lasserre, Agnes Nadjar, Djoher Nora Abrous, Sophie Laye, Daniela Cota
Cell proliferation and neuroinflammation in the adult hypothalamus may contribute to the pathogenesis of obesity. Here we tested whether the intertwining of these two processes has a role in the metabolic changes caused by three weeks of saturated high-fat diet (HFD) consumption.As compared to chow, HFD-fed mice rapidly increased body weight and fat mass, and specifically showed increased microglia number in the arcuate nucleus (ARC) of the hypothalamus. Microglia expansion required the adequate presence of fats and carbohydrates in the diet, since feeding mice a very high-fat, very low-carbohydrate diet did not affect cell proliferation...
November 30, 2016: Diabetes
https://www.readbyqxmd.com/read/27903651/t-cells-encountering-myeloid-cells-programmed-for-amino-acid-dependent-immunosuppression-use-rictor-mtorc2-for-proliferative-checkpoint-decisions
#12
Lee-Ann Van de Velde, Chitra Subramanian, Amber M Smith, Luke Barron, Joseph E Qualls, Geoffrey Neale, Adolfo Alfonso-Pecchio, Suzanne Jackowski, Charles O Rock, Thomas A Wynn, Peter J Murray
Modulation of T cell proliferation and function by immunoregulatory myeloid cells is an essential means of preventing self-reactivity and restoring tissue homeostasis. Consumption of amino acids such as arginine and tryptophan by immunoregulatory macrophages is one pathway that suppresses local T cell proliferation. Using a reduced complexity in vitro macrophage: T cell co-culture system, we show that macrophage Arginase-1 (Arg1) is the only factor required by M2 macrophages to block T cells in G1, and this effect is mediated by L-arginine elimination rather than metabolite generation...
November 30, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27901270/adipose-tissue-inflammation-by-intermittent-hypoxia-mechanistic-link-between-obstructive-sleep-apnoea-and-metabolic-dysfunction
#13
Silke Ryan
Obstructive sleep apnoea (OSA) is a highly prevalent condition and recognized as a major public health burden conveying a significant risk of cardiometabolic diseases and mortality. Type 2 diabetes (T2D), insulin resistance (IR) and glucose tolerance are common in subjects with OSA and this association is at least in part independent of the effects of obesity. Continuous positive airway pressure (CPAP) is the treatment of choice for the majority of patients with OSA but the benefit of CPAP on glycaemic health is uncertain...
November 29, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27895643/azithromycin-attenuates-pseudomonas-induced-lung-inflammation-by-targeting-bacterial-proteins-secreted-in-the-cultured-medium
#14
Teresinha Leal, Gabriella Bergamini, François Huaux, Nadtha Panin, Sabrina Noel, Barbara Dhooghe, Jeremy B Haaf, Pierluigi Mauri, Sara Motta, Dario Di Silvestre, Paola Melotti, Claudio Sorio
BACKGROUND: Pseudomonas aeruginosa airway infections are a major cause of morbidity and mortality in patients with cystic fibrosis (CF). Azithromycin improves the related clinical outcomes, but its mechanisms of action remain poorly understood. We tested the hypothesis that azithromycin downregulates P. aeruginosa-induced pro-inflammatory responses by modifying release of bacterial proteins. METHODS: We monitored inflammatory markers in lungs of CF mutant mice and their littermate controls in response to conditioned media (CM) collected from the reference P...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27895397/th17-involvement-in-nonalcoholic-fatty-liver-disease-progression-to-non-alcoholic-steatohepatitis
#15
REVIEW
Carla Melisa Chackelevicius, Sabrina Eliana Gambaro, Claudio Tiribelli, Natalia Rosso
The nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. NAFLD encompasses a wide histological spectrum ranging from benign simple steatosis to non-alcoholic steatohepatitis (NASH). Sustained inflammation in the liver is critical in this process. Hepatic macrophages, including liver resident macropaghes (Kupffer cells), monocytes infiltrating the injured liver, as well as specific lymphocytes subsets play a pivotal role in the initiation and perpetuation of the inflammatory response, with a major deleterious impact on the progression of fatty liver to fibrosis...
November 7, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27895089/oxidized-high-density-lipoprotein-induces-macrophage-apoptosis-via-toll-like-receptor-4-dependent-chop-pathway
#16
Shutong Yao, Hua Tian, Li Zhao, Jinguo Li, Libo Yang, Feng Yue, Yanyan Li, Peng Jiao, Nana Yang, Yiwei Wang, Xiangjian Zhang, Shucun Qin
Oxidized high-density lipoprotein (ox-HDL), unlike native HDL that exerts antiatherogenic effects, plays a proatherogenic role. However, the underlying mechanisms are not completely understood. This study was designed to explore the inductive effect of ox-HDL on endoplasmic reticulum (ER) stress-C/EBP homologous protein (CHOP)-mediated macrophage apoptosis and its upstream mechanisms. Our results showed that ox-HDL could be ingested by macrophages, causing intracellular lipid accumulation. Like tunicamycin (an ER stress inducer), ox-HDL induced macrophage apoptosis with concomitant activation of ER stress pathway, including nuclear translocation of activating transcription factor 6, phosphorylation of protein kinase-like ER kinase and eukaryotic translation initiation factor 2α, and upregulation of glucose regulated protein 78 and CHOP, which were inhibited by 4-phenylbutyric acid (PBA, an ER stress inhibitor) and CHOP gene silencing...
November 28, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27890613/activation-of-ppar%C3%AE-does-not-contribute-to-macrophage-abca1-expression-and-abca1-mediated-cholesterol-efflux-to-apoai
#17
Meixiu Jiang, Xiaoju Li
Activation of macrophage ABCA1/G1 expression and cholesterol efflux is believed one of the mechanisms by which PPARγ inhibits atherosclerosis. PPARγ can also activate CD36 expression, a receptor for oxLDL, which may supply LXR ligands to activate LXR-ABCA1/G1 pathways. However, the controversial effects of PPARγ on ABCA1 expression have been reported. In this study, we used peritoneal macrophages isolated from wild type and CD36 deficient (CD36(-/-)) mice to clarify if PPARγ ligands can influence ABCA1 expression by CD36 function...
November 24, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27889764/high-uric-acid-activates-the-ros-ampk-pathway-impairs-cd68-expression-and-inhibits-oxldl-induced-foam-cell-formation-in-a-human-monocytic-cell-line-thp-1
#18
Chaohuan Luo, Xueke Lian, Liangli Hong, Jingfang Zou, Zhi Li, Yuzhang Zhu, Tianliang Huang, Yongneng Zhang, Yaqiu Hu, Huier Yuan, Tengfei Wen, Wanling Zhuang, Bozhi Cai, Xin Zhang, Ichiro Hisatome, Tetsuya Yamamoto, Jiexiong Huang, Jidong Cheng
BACKGROUND/AIMS: Hyperuricemia is part of the metabolic-syndrome cluster of abdominal obesity, impaired glucose tolerance, insulin resistance, dyslipidemia, and hypertension. Monocytes/macrophages are critical in the development of metabolic syndrome, including gout, obesity and atherosclerosis. However, how high uric acid (HUA) exposure affects monocyte/macrophage function remains unclear. In this study, we investigated the molecular mechanism of HUA exposure in monocytes/macrophages and its impact on oxidized low-density lipoprotein (oxLDL)-induced foam-cell formation in a human monocytic cell line, THP-1...
November 25, 2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27887857/a-potential-contribution-of-dipeptidyl-peptidase-4-by-the-mediation-of-monocyte-differentiation-in-the-development-and-progression-of-abdominal-aortic-aneurysms
#19
Hsin-Ying Lu, Chun-Yao Huang, Chun-Ming Shih, Yi-Wen Lin, Chein-Sung Tsai, Feng-Yen Lin, Chun-Che Shih
OBJECTIVE: Abdominal aortic aneurysms (AAAs) are characterized by the destruction of elastin and collagen in the media and adventitia. Dipeptidyl peptidase-4 (DPP-4, an adipokine known as CD26) influences cell signaling, cell-matrix interactions, and the regulation of the functional activity of incretins in metabolic and inflammatory disorders. Although the role of DPP-4 in AAA evolution has been demonstrated, the underlying mechanisms of DPP-4-regulated AAA development remains unknown...
November 22, 2016: Journal of Vascular Surgery
https://www.readbyqxmd.com/read/27887776/critical-role-of-superoxide-anions-and-hydroxyl-radicals-in-hema-induced-apoptosis
#20
H Schweikl, M Godula, C Petzel, C Bolay, K A Hiller, W Buchalla
OBJECTIVE: Resin monomers such as 2-hydroxyethyl methacrylate (HEMA) induce apoptosis because of the excess formation of reactive oxygen species (ROS). The portion of ROS including superoxide anions, hydrogen peroxide or hydroxyl radicals in monomer-induced apoptosis is unknown. Here, the effectiveness of superoxide anions or hydroxyl radicals was analyzed using tempol or sodium formate as radical scavengers. METHODS: RAW264.7 mouse macrophages were exposed to HEMA (0-6-8mM) in the presence of tempol (0-0...
November 22, 2016: Dental Materials: Official Publication of the Academy of Dental Materials
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