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Macrophage metabolism

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https://www.readbyqxmd.com/read/29785785/metabolism-within-the-tumor-microenvironment-and-its-implication-on-cancer-progression-an-ongoing-therapeutic-target
#1
REVIEW
Ma Carmen Ocaña, Beatriz Martínez-Poveda, Ana R Quesada, Miguel Ángel Medina
Since reprogramming energy metabolism is considered a new hallmark of cancer, tumor metabolism is again in the spotlight of cancer research. Many studies have been carried out and many possible therapies have been developed in the last years. However, tumor cells are not alone. A series of extracellular components and stromal cells, such as endothelial cells, cancer-associated fibroblasts, tumor-associated macrophages, and tumor-infiltrating T cells, surround tumor cells in the so-called tumor microenvironment (TME)...
May 22, 2018: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29785241/an-in-vivo-zebrafish-model-for-interrogating-ros-mediated-pancreatic-%C3%AE-cell-injury-response-and-prevention
#2
Abhishek A Kulkarni, Abass M Conteh, Cody A Sorrell, Anjali Mirmira, Sarah A Tersey, Raghavendra G Mirmira, Amelia K Linnemann, Ryan M Anderson
It is well known that a chronic state of elevated reactive oxygen species (ROS) in pancreatic β -cells impairs their ability to release insulin in response to elevated plasma glucose. Moreover, at its extreme, unmitigated ROS drives regulated cell death. This dysfunctional state of ROS buildup can result both from genetic predisposition and environmental factors such as obesity and overnutrition. Importantly, excessive ROS buildup may underlie metabolic pathologies such as type 2 diabetes mellitus. The ability to monitor ROS dynamics in β -cells in situ and to manipulate it via genetic, pharmacological, and environmental means would accelerate the development of novel therapeutics that could abate this pathology...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29784886/-legionella-pneumophila-is-directly-sensitive-to-2-deoxyglucose-phosphate-via-its-uhpc-transporter-but-is-indifferent-to-shifts-in-host-cell-glycolytic-metabolism
#3
Jordan V Price, Kallie Jiang, Abigail Galantowicz, Alana Freifeld, Russell E Vance
Toll-like receptor stimulation induces a pronounced shift to increased glycolytic metabolism in mammalian macrophages. We observed that bone marrow-derived macrophages (BMMs) increase glycolysis in response to infection with Legionella pneumophila ( L. pneumophila ), but the role of host macrophage glycolysis on intracellular L. pneumophila replication is not currently understood. Treatment with 2-deoxyglucose (2DG) blocks L. pneumophila replication in mammalian macrophages but has no effect on bacteria grown in broth...
May 21, 2018: Journal of Bacteriology
https://www.readbyqxmd.com/read/29780382/extracellular-purine-metabolism-is-the-switchboard-of-immunosuppressive-macrophages-and-a-novel-target-to-treat-diseases-with-macrophage-imbalances
#4
Anna Ohradanova-Repic, Christian Machacek, Celine Charvet, Franck Lager, Delphine Le Roux, René Platzer, Vladimir Leksa, Goran Mitulovic, Thomas R Burkard, Gerhard J Zlabinger, Michael B Fischer, Vincent Feuillet, Gilles Renault, Stephan Blüml, Miroslav Benko, Miloslav Suchanek, Johannes B Huppa, Takami Matsuyama, Artur Cavaco-Paulo, Georges Bismuth, Hannes Stockinger
If misregulated, macrophage (Mϕ)-T cell interactions can drive chronic inflammation thereby causing diseases, such as rheumatoid arthritis (RA). We report that in a proinflammatory environment, granulocyte-Mϕ (GM-CSF)- and Mϕ colony-stimulating factor (M-CSF)-dependent Mϕs have dichotomous effects on T cell activity. While GM-CSF-dependent Mϕs show a highly stimulatory activity typical for M1 Mϕs, M-CSF-dependent Mϕs, marked by folate receptor β (FRβ), adopt an immunosuppressive M2 phenotype. We find the latter to be caused by the purinergic pathway that directs release of extracellular ATP and its conversion to immunosuppressive adenosine by co-expressed CD39 and CD73...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29779612/origin-and-specialization-of-splenic-macrophages
#5
Noelia A-Gonzalez, Antonio Castrillo
Macrophage heterogeneity in the spleen has been long documented, with four subsets populating the different splenic compartments. The diverse environments on the splenic compartments determine their varied phenotype and functions. In the white pulp, highly phagocytic macrophages contribute to the generation of the immune response. The marginal zone contains two populations of macrophages, which also contribute to the immune response. Their strategic position in the bloodstream and their unique phenotype confer them a crucial role in the defense against blood borne pathogens, placing them at the crossroad between innate and adaptive immune responses...
May 15, 2018: Cellular Immunology
https://www.readbyqxmd.com/read/29777213/semaphorin-6d-reverse-signaling-controls-macrophage-lipid-metabolism-and-anti-inflammatory-polarization
#6
Sujin Kang, Yoshimitsu Nakanishi, Yoshiyuki Kioi, Daisuke Okuzaki, Tetsuya Kimura, Hyota Takamatsu, Shohei Koyama, Satoshi Nojima, Masayuki Nishide, Yoshitomo Hayama, Yuhei Kinehara, Yasuhiro Kato, Takeshi Nakatani, Tomomi Shimogori, Junichi Takagi, Toshihiko Toyofuku, Atsushi Kumanogoh
Polarization of macrophages into pro-inflammatory or anti-inflammatory states has distinct metabolic requirements, with mechanistic target of rapamycin (mTOR) kinase signaling playing a critical role. However, it remains unclear how mTOR regulates metabolic status to promote polarization of these cells. Here we show that an mTOR-Semaphorin 6D (Sema6D)-Peroxisome proliferator receptor γ (PPARγ) axis plays critical roles in macrophage polarization. Inhibition of mTOR or loss of Sema6D blocked anti-inflammatory macrophage polarization, concomitant with severe impairments in PPARγ expression, uptake of fatty acids, and lipid metabolic reprogramming...
May 18, 2018: Nature Immunology
https://www.readbyqxmd.com/read/29777212/regulation-of-macrophage-immunometabolism-in-atherosclerosis
#7
REVIEW
Graeme J Koelwyn, Emma M Corr, Ebru Erbay, Kathryn J Moore
After activation, cells of the myeloid lineage undergo robust metabolic transitions, as well as discrete epigenetic changes, that can dictate both ongoing and future inflammatory responses. In atherosclerosis, in which macrophages play central roles in the initiation, growth, and ultimately rupture of arterial plaques, altered metabolism is a key feature that dictates macrophage function and subsequent disease progression. This Review explores how factors central to the plaque microenvironment (for example, altered cholesterol metabolism, oxidative stress, hypoxia, apoptotic and necrotic cells, and hyperglycemia) shape the metabolic rewiring of macrophages in atherosclerosis as well as how these metabolic shifts in turn alter macrophage immune-effector and tissue-reparative functions...
May 18, 2018: Nature Immunology
https://www.readbyqxmd.com/read/29773345/t-cells-and-their-immunometabolism-a-novel-way-to-understanding-sepsis-immunopathogenesis-and-future-therapeutics
#8
REVIEW
V Kumar
Sepsis has always been considered as a big challenge for pharmaceutical companies in terms of discovering and designing new therapeutics. The pathogenesis of sepsis involves aberrant activation of innate immune cells (i.e. macrophages, neutrophils etc.) at early stages. However, a stage of immunosuppression is also observed during sepsis even in the patients who have recovered from it. This stage of immunosuppression is observed due to the loss of conventional (i.e. CD4+ , CD8+ ) T cells, Th17 cells and an upregulation of regulatory T cells (Tregs)...
May 5, 2018: European Journal of Cell Biology
https://www.readbyqxmd.com/read/29773170/iron-and-innate-antimicrobial-immunity-depriving-the-pathogen-defending-the-host
#9
REVIEW
Manfred Nairz, Stefanie Dichtl, Andrea Schroll, David Haschka, Piotr Tymoszuk, Igor Theurl, Günter Weiss
The acute-phase response is triggered by the presence of infectious agents and danger signals which indicate hazards for the integrity of the mammalian body. One central feature of this response is the sequestration of iron into storage compartments including macrophages. This limits the availability of this essential nutrient for circulating pathogens, a host defence strategy known as 'nutritional immunity'. Iron metabolism and the immune response are intimately linked. In infections, the availability of iron affects both the efficacy of antimicrobial immune pathways and pathogen proliferation...
July 2018: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/29771935/cell-iron-status-influences-macrophage-polarization
#10
Rafiou Agoro, Meriem Taleb, Valerie F J Quesniaux, Catherine Mura
Macrophages play crucial roles in innate immune response and in the priming of adaptive immunity, and are characterized by their phenotypic heterogeneity and plasticity. Reprogramming intracellular metabolism in response to microenvironmental signals is required for M1/M2 macrophage polarization and function. Here we assessed the influence of iron on the polarization of the immune response in vivo and in vitro. Iron-enriched diet increased M2 marker Arg1 and Ym1 expression in liver and peritoneal macrophages, while iron deficiency decreased Arg1 expression...
2018: PloS One
https://www.readbyqxmd.com/read/29771915/inactivation-of-bpsl1039-1040-atp-binding-cassette-transporter-reduces-intracellular-survival-in-macrophages-biofilm-formation-and-virulence-in-the-murine-model-of-burkholderia-pseudomallei-infection
#11
Peechanika Pinweha, Pornpan Pumirat, Jon Cuccui, Niramol Jitprasutwit, Veerachat Muangsombut, Varintip Srinon, Usa Boonyuen, Parameth Thiennimitr, Paiboon Vattanaviboon, Felipe Cia, Sam Willcocks, Gregory J Bancroft, Brendan W Wren, Sunee Korbsrisate
Burkholderia pseudomallei, a gram-negative intracellular bacillus, is the causative agent of a tropical infectious disease called melioidosis. Bacterial ATP-binding cassette (ABC) transporters import and export a variety of molecules across bacterial cell membranes. At present, their significance in B. pseudomallei pathogenesis is poorly understood. We report here characterization of the BPSL1039-1040 ABC transporter. B. pseudomallei cultured in M9 medium supplemented with nitrate, demonstrated that BPSL1039-1040 is involved in nitrate transport for B...
2018: PloS One
https://www.readbyqxmd.com/read/29770796/suppression-of-mif-induced-neuronal-apoptosis-may-underlie-the-therapeutic-effects-of-effective-components-of-fufang-danshen-in-the-treatment-of-alzheimer-s-disease
#12
Cheng-Jie Liang, Jia-Huang Li, Zhen Zhang, Ju-Yan Zhang, Shu-Qun Liu, Jie Yang
Fufang Danshen (FFDS or Compound Danshen) consists of three Chinese herbs Danshen (Salviae miltiorrhizae radix et rhizome), Sanqi (Notoginseng radix et rhizome) and Tianranbingpian (Borneolum, or D-borneol), which has been show to significantly improve the function of the nervous system and brain metabolism. In this study we explored the possible mechanisms underlying the therapeutic effects of the combination of the effective components of FFDS (Tan IIA, NG-R1 and Borneol) in the treatment of Alzheimer's disease (AD) based on network pharmacology...
May 17, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29768197/induction-of-nitric-oxide-metabolism-in-enterocytes-alleviates-colitis-and-inflammation-associated-colon-cancer
#13
Noa Stettner, Chava Rosen, Biana Bernshtein, Shiri Gur-Cohen, Julia Frug, Alon Silberman, Alona Sarver, Narin N Carmel-Neiderman, Raya Eilam, Inbal Biton, Meirav Pevsner-Fischer, Niv Zmora, Alexander Brandis, Keren Bahar Halpern, Ram Mazkereth, Diego di Bernardo, Nicola Brunetti-Pierri, Muralidhar H Premkumar, Gillian Dank, Sandesh C S Nagamani, Steffen Jung, Alon Harmelin, Ayelet Erez
Nitric oxide (NO) plays an established role in numerous physiological and pathological processes, but the specific cellular sources of NO in disease pathogenesis remain unclear, preventing the implementation of NO-related therapy. Argininosuccinate lyase (ASL) is the only enzyme able to produce arginine, the substrate for NO generation by nitric oxide synthase (NOS) isoforms. Here, we generated cell-specific conditional ASL knockout mice in combination with genetic and chemical colitis models. We demonstrate that NO derived from enterocytes alleviates colitis by decreasing macrophage infiltration and tissue damage, whereas immune cell-derived NO is associated with macrophage activation, resulting in increased severity of inflammation...
May 15, 2018: Cell Reports
https://www.readbyqxmd.com/read/29768180/dietary-fiber-confers-protection-against-flu-by-shaping-ly6c-patrolling-monocyte-hematopoiesis-and-cd8-t-cell-metabolism
#14
Aurélien Trompette, Eva S Gollwitzer, Céline Pattaroni, Isabel C Lopez-Mejia, Erika Riva, Julie Pernot, Niki Ubags, Lluis Fajas, Laurent P Nicod, Benjamin J Marsland
Dietary fiber protects against chronic inflammatory diseases by dampening immune responses through short-chain fatty acids (SCFAs). Here we examined the effect of dietary fiber in viral infection, where the anti-inflammatory properties of SCFAs in principle could prevent protective immunity. Instead, we found that fermentable dietary fiber increased survival of influenza-infected mice through two complementary mechanisms. High-fiber diet (HFD)-fed mice exhibited altered bone marrow hematopoiesis, characterized by enhanced generation of Ly6c- patrolling monocytes, which led to increased numbers of alternatively activated macrophages with a limited capacity to produce the chemokine CXCL1 in the airways...
May 15, 2018: Immunity
https://www.readbyqxmd.com/read/29766296/characterization-of-in-vivo-metabolites-in-rat-urine-following-an-oral-dose-of-masitinib-by-liquid-chromatography-tandem-mass-spectrometry
#15
Adnan A Kadi, Sawsan M Amer, Hany W Darwish, Mohamed W Attwa
Masitinib (MST) is an orally administered drug that targets mast cells and macrophages, important cells for immunity, by inhibiting a limited number of tyrosine kinases. It is currently registered in Europe and USA for the treatment of mast cell tumors in dogs. AB Science announced that the European Medicines Agency has accepted a conditional marketing authorization application for MST to treat amyotrophic lateral sclerosis. In our work, we focused on studying in vivo metabolism of MST in Sprague-Dawley rats...
May 15, 2018: Chemistry Central Journal
https://www.readbyqxmd.com/read/29765984/jazf1-inhibits-adipose-tissue-macrophages-and-adipose-tissue-inflammation-in-diet-induced-diabetic-mice
#16
Fanping Meng, Yao Lin, Min Yang, Minyan Li, Gangyi Yang, Po Hao, Ling Li
Background: Juxtaposed with another zinc finger gene 1 (JAZF1) affects gluconeogenesis, insulin sensitivity, lipid metabolism, and inflammation, but its exact role in chronic inflammation remains unclear. This study aimed to examine JAZF1 overexpression in vivo on adipose tissue macrophages (ATMs). Methods: Mouse models of high-fat diet- (HFD-) induced insulin resistance were induced using C57BL/6J and JAZF1-overexpressing (JAZF1-OX) mice. The mice were randomized (8-10/group) to C57BL/6J mice fed regular diet (RD) (NC group), C57BL/6J mice fed HFD (HF group), JAZF1-OX mice fed RD (NJ group), and JAZF1-OX mice fed HFD (HJ group)...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29765489/gallic-acid-l-leucine-conjugate-protects-mice-against-lps-induced-inflammation-and-sepsis-via-correcting-proinflammatory-lipid-mediator-profiles-and-oxidative-stress
#17
Yuanyuan Cheng, Xuechen Li, Hung-Fat Tse, Jianhui Rong
The pathology of endotoxin LPS-induced sepsis is hallmarked by aberrant production of proinflammatory lipid mediators and nitric oxide (NO). The aim of the present study was to determine whether the new product gallic acid-L-leucine (GAL) conjugate could ameliorate the LPS-induced dysregulation of arachidonic acid metabolism and NO production. We first investigated the effects of GAL conjugate on the expression of proinflammatory enzymes and the production of proinflammatory NO and lipid mediators in mouse macrophage cell line RAW264...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29762555/global-transcriptome-analysis-identifies-weight-regain-induced-activation-of-adaptive-immune-responses-in-white-adipose-tissue-of-mice
#18
D S Kyung, H R Sung, Y J Kim, K D Kim, S Y Cho, J H Choi, Y-H Lee, I Y Kim, J K Seong
OBJECTIVE: Studies have indicated that weight regain following weight loss predisposes obese individuals to metabolic disorders; however, the molecular mechanism of this potential adverse effect of weight regain is not fully understood. Here we investigated global transcriptome changes and the immune response in mouse white adipose tissue caused by weight regain. DESIGN: We established a diet switch protocol to compare the effects of weight regain with those of weight gain without precedent weight loss, weight loss maintenance and chow diet...
December 7, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29761170/nicotinamide-adenine-dinucleotide-phosphate-reduced-oxidase-2-modulates-inflammatory-vigor-during-nonalcoholic-fatty-liver-disease-progression-in-mice
#19
Rajib Mukherjee, Maria E Moreno-Fernandez, Daniel A Giles, Monica Cappelletti, Traci E Stankiewicz, Calvin C Chan, Senad Divanovic
Nonalcoholic fatty liver disease (NAFLD) represents a disease spectrum ranging from benign steatosis to life-threatening cirrhosis and hepatocellular carcinoma. Elevated levels of reactive oxygen species (ROS) and exacerbated inflammatory responses have been implicated in NAFLD progression. Nicotinamide adenine dinucleotide phosphate (reduced) oxidase 2 (NOX2; also known as gp91Phox ), the main catalytic subunit of the nicotinamide adenine dinucleotide phosphate (reduced) oxidase complex, modulates ROS production, immune responsiveness, and pathogenesis of obesity-associated metabolic derangements...
May 2018: Hepatology Communications
https://www.readbyqxmd.com/read/29760217/temporal-manipulation-of-mitochondrial-function-by-virulent-francisella-tularensis-to-limit-inflammation-and-control-cell-death
#20
Forrest Jessop, Benjamin Schwarz, Emily Heitmann, Robert Buntyn, Tara Wehrly, Catharine M Bosio
Francisella tularensis ssp tularensis (Ftt) is a highly pathogenic intracellular bacterium that suppresses host inflammation by impairing the metabolic shift from oxidative phosphorylation to glycolysis. Decreased mitochondrial metabolism is central to initiating a metabolic shift to glycolysis and regulating inflammation, but Ftt manipulation of host mitochondrial function has not been explored. We demonstrate using extracellular flux analysis that Ftt infection initially improves host macrophage mitochondrial bioenergetics in a capsule dependent manner...
May 14, 2018: Infection and Immunity
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