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Immune glycolysis

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https://www.readbyqxmd.com/read/28213330/drug-discovery-strategies-in-the-field-of-tumor-energy-metabolism-limitations-by-metabolic-flexibility-and-metabolic-resistance-to-chemotherapy
#1
REVIEW
N D Amoedo, E Obre, R Rossignol
The search for new drugs capable of blocking the metabolic vulnerabilities of human tumors has now entered the clinical evaluation stage, but several projects already failed in phase I or phase II. In particular, very promising in vitro studies could not be translated in vivo at preclinical stage and beyond. This was the case for most glycolysis inhibitors that demonstrated systemic toxicity. A more recent example is the inhibition of glutamine catabolism in lung adenocarcinoma that failed in vivo despite a strong addiction of several cancer cell lines to glutamine in vitro...
February 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28212523/redox-regulation-in-metabolic-programming-and-inflammation
#2
REVIEW
Helen R Griffiths, Dan Gao, Chathyan Pararasa
Energy metabolism and redox state are intrinsically linked. In order to mount an adequate immune response, cells must have an adequate and rapidly available energy resource to migrate to the inflammatory site, to generate reactive oxygen species using NADPH as a cofactor and to engulf bacteria or damaged tissue. The first responder cells of the innate immune response, neutrophils, are largely dependent on glycolysis. Neutrophils are relatively short-lived, dying via apoptosis in the process of bacterial killing through production of hypochlorous acid and release of extracellular NETs...
February 12, 2017: Redox Biology
https://www.readbyqxmd.com/read/28186160/3-bromopyruvate-ameliorate-autoimmune-arthritis-by-modulating-th17-treg-cell-differentiation-and-suppressing-dendritic-cell-activation
#3
Takaichi Okano, Jun Saegusa, Keisuke Nishimura, Soshi Takahashi, Sho Sendo, Yo Ueda, Akio Morinobu
Recent studies have shown that cellular metabolism plays an important role in regulating immune cell functions. In immune cell differentiation, both interleukin-17-producing T (Th17) cells and dendritic cells (DCs) exhibit increased glycolysis through the upregulation of glycolytic enzymes, such as hexokinase-2 (HK2). Blocking glycolysis with 2-deoxyglucose was recently shown to inhibit Th17 cell differentiation while promoting regulatory T (Treg) cell generation. However, 2-DG inhibits all isoforms of HK. Thus, it is unclear which isoform has a critical role in Th17 cell differentiation and in rheumatoid arthritis (RA) pathogenesis...
February 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28154172/metabolic-alterations-contribute-to-enhanced-inflammatory-cytokine-production-in-irgm1-deficient-macrophages
#4
Elyse A Schmidt, Brian E Fee, Stanley C Henry, Amanda G Nichols, Mari L Shinohara, Jeffrey C Rathmell, Nancie J MacIver, Jörn Coers, Olga R Ilkayeva, Timothy R Koves, Gregory A Taylor
The Immunity-Related GTPases (IRG) are a family of proteins that are induced by interferon (IFN)-gamma and play pivotal roles in immune and inflammatory responses. IRGs ostensibly function as dynamin-like proteins that bind to intracellular membranes, and promote remodeling and trafficking of those membranes. Prior studies have shown that loss of Irgm1 in mice leads to increased lethality to bacterial infections, as well as enhanced inflammation to non-infectious stimuli; however, the mechanisms underlying these phenotypes are unclear...
February 1, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28138373/resistance-of-candida-albicans-biofilms-to-drugs-and-the-host-immune-system
#5
REVIEW
Doblin Sandai, Yasser M Tabana, Ahmad El Ouweini, Ishola Oluwaseun Ayodeji
BACKGROUND: Candida albicans is a commensal fungus that resides on mucosal surfaces and in the gastrointestinal and genitourinary tracts in humans. However, it can cause an infection when the immune system of the host is impaired or if a niche becomes available. Many C. albicans infections are due to the organism's ability to form a biofilm on implanted medical devices. A biofilm represents an optimal medium for the growth of C. albicans as it allows cells to be enclosed by a self-produced extracellular matrix (ECM)...
November 2016: Jundishapur Journal of Microbiology
https://www.readbyqxmd.com/read/28130076/glycolysis-regulates-lps-induced-cytokine-production-in-m2-polarized-human-macrophages
#6
Sayako Chiba, Tadakazu Hisamatsu, Hiroaki Suzuki, Kiyoto Mori, Mina T Kitazume, Katsuyoshi Shimamura, Shinta Mizuno, Nobuhiro Nakamoto, Katsuyoshi Matsuoka, Makoto Naganuma, Takanori Kanai
M1 and M2 macrophages are the key players in innate immunity, and are associated with tissue homeostasis and diseases. Although M2 macrophages are known to depend on fatty acid oxidation (FAO) for their activation, how metabolic pathways affect the production of each cytokine induced by pathogen or bacterial components is unclear. Here, we examined the role of the glycolytic pathway in M2 polarized human macrophages in cytokine production induced by lipopolysaccharide (LPS) stimulation. Human monocytes were isolated from peripheral blood by positive selection for CD14 expression and cultured with macrophage colony-stimulating factor (M-CSF), to obtain M-CSF-induced macrophages (M-MΦ)...
January 24, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28115589/targeting-metabolism-as-a-novel-therapeutic-approach-to-autoimmunity-inflammation-and-transplantation
#7
REVIEW
Ian A Bettencourt, Jonathan D Powell
Immune cell activation and differentiation occurs concurrently with metabolic reprogramming. This ensures that activated cells generate the energy and substrates necessary to perform their specified function. Likewise, the metabolic programs among different cells of the immune system vary. By targeting different metabolic pathways, these differences allow for selective regulation of immune responses. Further, the relative susceptibility of cells to a metabolic inhibitor is dictated by their metabolic demands; cellular selectivity is based on demand...
February 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28115529/the-insulin-receptor-plays-a-critical-role-in-t-cell-function-and-adaptive-immunity
#8
Henrike J Fischer, Christopher Sie, Eric Schumann, Ann-Kathrin Witte, Ralf Dressel, Jens van den Brandt, Holger M Reichardt
T cell activation is an energy-demanding process fueled by increased glucose consumption and accompanied by upregulation of the insulin receptor (INSR). In this article, we report that silencing the INSR in inducible knockdown rats impairs selective T cell functions but not thymocyte development. Glucose transport and glycolysis in activated CD4(+) T cells were compromised in the absence of the INSR, which was associated with alterations in intracellular signaling pathways. The observed metabolic defects coincided with reduced cytokine production, proliferation, and migration, as well as increased apoptosis of CD4(+) T cells...
January 23, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28109606/short-communication-glutamine-modulates-inflammatory-responses-to-lipopolysaccharide-in-ex-vivo-bovine-endometrium
#9
Pablo G Noleto, João Paulo E Saut, I Martin Sheldon
Bacteria infect the endometrium lining the uterus of cattle after parturition, and clearance of these microbes depends on a robust innate immune response to bacterial molecules, such as the endotoxin lipopolysaccharide (LPS). Endometrial inflammation is characterized by secretion of the cytokines IL-1β and IL-6 and the chemokine IL-8. However, animals often fail to clear invading bacteria and develop uterine disease if they are in negative energy balance, with reduced abundance of glucose and glutamine, which are substrates for energy in tissues...
March 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28069950/chronic-innate-immune-activation-of-tbk1-suppresses-mtorc1-activity-and-dysregulates-cellular-metabolism
#10
Maroof Hasan, Vijay K Gonugunta, Nicole Dobbs, Aktar Ali, Guillermo Palchik, Maria A Calvaruso, Ralph J DeBerardinis, Nan Yan
Three-prime repair exonuclease 1 knockout (Trex1(-/-)) mice suffer from systemic inflammation caused largely by chronic activation of the cyclic GMP-AMP synthase-stimulator of interferon genes-TANK-binding kinase-interferon regulatory factor 3 (cGAS-STING-TBK1-IRF3) signaling pathway. We showed previously that Trex1-deficient cells have reduced mammalian target of rapamycin complex 1 (mTORC1) activity, although the underlying mechanism is unclear. Here, we performed detailed metabolic analysis in Trex1(-/-) mice and cells that revealed both cellular and systemic metabolic defects, including reduced mitochondrial respiration and increased glycolysis, energy expenditure, and fat metabolism...
January 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28051265/the-role-of-hypoxia-inducible-factor-in-nasal-inflammations
#11
K-J Cheng, Y-Y Bao, S-H Zhou
OBJECTIVE: Hypoxia-inducible factor (HIF) is considered an important transcription factor due to its roles in glycolysis, angiogenesis, cell differentiation, apoptosis, and other cellular pathways. It takes the role in various physiological and pathological states, such as solid tumors, vascular injury, and atherosclerotic lesion progression. In recent studies, HIF is found as a master regulator of body inflammation and immunity, not only in hypoxia but also in normoxia. Nasal inflammation has a close relationship with anoxia...
December 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28030896/cancer-metabolism-fueling-more-than-just-growth
#12
REVIEW
Namgyu Lee, Dohoon Kim
The early landmark discoveries in cancer metabolism research have uncovered metabolic processes that support rapid proliferation, such as aerobic glycolysis (Warburg effect), glutaminolysis, and increased nucleotide biosynthesis. However, there are limitations to the effectiveness of specifically targeting the metabolic processes which support rapid proliferation. First, as other normal proliferative tissues also share similar metabolic features, they may also be affected by such treatments. Secondly, targeting proliferative metabolism may only target the highly proliferating "bulk tumor" cells and not the slower-growing, clinically relevant cancer stem cell subpopulations which may be required for an effective cure...
December 2016: Molecules and Cells
https://www.readbyqxmd.com/read/27993896/reexamining-cancer-metabolism-lactate-production-for-carcinogenesis-could-be-the-purpose-and-explanation-of-the-warburg-effect
#13
REVIEW
Iñigo San-Millán, George A Brooks
Herein, we use lessons learned in exercise physiology and metabolism to propose that augmented lactate production ('lactagenesis'), initiated by gene mutations, is the reason and purpose of the Warburg Effect and that dysregulated lactate metabolism and signaling are the key elements in carcinogenesis. Lactate-producing ('lactagenic') cancer cells are characterized by increased aerobic glycolysis and excessive lactate formation, a phenomenon described by Otto Warburg 93 years ago, which still remains unexplained...
December 17, 2016: Carcinogenesis
https://www.readbyqxmd.com/read/27991883/microbial-stimulation-of-different-toll-like-receptor-signalling-pathways-induces-diverse-metabolic-programmes-in-human-monocytes
#14
Ekta Lachmandas, Lily Boutens, Jacqueline M Ratter, Anneke Hijmans, Guido J Hooiveld, Leo A B Joosten, Richard J Rodenburg, Jack A M Fransen, Riekelt H Houtkooper, Reinout van Crevel, Mihai G Netea, Rinke Stienstra
Microbial stimuli such as lipopolysaccharide (LPS) induce robust metabolic rewiring in immune cells known as the Warburg effect. It is unknown whether this increase in glycolysis and decrease in oxidative phosphorylation (OXPHOS) is a general characteristic of monocytes that have encountered a pathogen. Using CD14(+) monocytes from healthy donors, we demonstrated that most microbial stimuli increased glycolysis, but that only stimulation of Toll-like receptor (TLR) 4 with LPS led to a decrease in OXPHOS. Instead, activation of other TLRs, such as TLR2 activation by Pam3CysSK4 (P3C), increased oxygen consumption and mitochondrial enzyme activity...
December 19, 2016: Nature Microbiology
https://www.readbyqxmd.com/read/27926861/immunometabolic-pathways-in-bcg-induced-trained-immunity
#15
Rob J W Arts, Agostinho Carvalho, Claudia La Rocca, Carla Palma, Fernando Rodrigues, Ricardo Silvestre, Johanneke Kleinnijenhuis, Ekta Lachmandas, Luís G Gonçalves, Ana Belinha, Cristina Cunha, Marije Oosting, Leo A B Joosten, Giuseppe Matarese, Reinout van Crevel, Mihai G Netea
The protective effects of the tuberculosis vaccine Bacillus Calmette-Guerin (BCG) on unrelated infections are thought to be mediated by long-term metabolic changes and chromatin remodeling through histone modifications in innate immune cells such as monocytes, a process termed trained immunity. Here, we show that BCG induction of trained immunity in monocytes is accompanied by a strong increase in glycolysis and, to a lesser extent, glutamine metabolism, both in an in-vitro model and after vaccination of mice and humans...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27926518/higher-programmed-cell-death-1-ligand-1-pd-l1-mrna-level-in-clear-cell-renal-cell-carcinomas-is-associated-with-a-favorable-outcome-due-to-the-active-immune-responses-in-tumor-tissues
#16
Xiang-Hui Ning, Yan-Qing Gong, Shi-Ming He, Teng Li, Jiang-Yi Wang, Shuang-He Peng, Jin-Chao Chen, Jia-Yuan Liu, Nie-Nie Qi, Ying-Lu Guo, Kan Gong
Renal cell carcinoma is one of the most common urological tumors. The role of programmed cell death 1 ligand 1 (PD-L1) in renal cell carcinomas in predicting outcome of the patients is yet unclear. We analyzed the clinical and RNA-seq data of 522 kidney clear cell cancer, 259 kidney papillary cell carcinoma and 66 kidney chromophobe patients from The Cancer Genome Atlas (TCGA) database. In kidney clear cell cancer patients with high PD-L1 mRNA level and low PD-L1 mRNA level in tumors, the median overall survival periods were 45...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/27918097/sugars-and-fat-a-healthy-way-to-generate-functional-regulatory-t-cells
#17
Sarah Sharon Gabriel, Axel Kallies
Cellular metabolism has emerged as an important regulator of adaptive immunity. While the metabolic requirements of conventional T cells are increasingly understood, the role of cellular metabolism in Foxp3(+) regulatory T (Treg) cells is less clear. Although it is well accepted that repression of Akt/mTOR, HIF-1α and aerobic glycolysis are important for the efficient generation of Treg cells in vitro, clear evidence how these pathways impact on Treg-cell development in vivo is limited. Furthermore, newer studies have shown that the same pathways that appear to suppress Treg-cell development are active in and required for functionally mature Treg cells...
December 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27911401/an-optimized-protocol-to-analyze-glycolysis-and-mitochondrial-respiration-in-lymphocytes
#18
Javier Traba, Pietro Miozzo, Billur Akkaya, Susan K Pierce, Munir Akkaya
Lymphocytes respond to a variety of stimuli by activating intracellular signaling pathways, which in turn leads to rapid cellular proliferation, migration and differentiation, and cytokine production. All of these events are tightly linked to the energy status of the cell, and therefore studying the energy-producing pathways may give clues about the overall functionality of these cells. The extracellular flux analyzer is a commonly used device for evaluating the performance of glycolysis and mitochondrial respiration in many cell types...
November 21, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27910764/metabolic-regulation-of-natural-killer-cell-ifn-%C3%AE-production
#19
Annelise Y Mah, Megan A Cooper
Metabolism is critical for a host of cellular functions and provides a source of intracellular energy. It has been recognized recently that metabolism also regulates differentiation and effector functions of immune cells. Although initial work in this field has focused largely on T lymphocytes, recent studies have demonstrated metabolic control of innate immune cells, including natural killer (NK) cells. Here, we review what is known regarding the metabolic requirements for NK cell activation, focusing on NK cell production of interferon-gamma (IFN-γ)...
2016: Critical Reviews in Immunology
https://www.readbyqxmd.com/read/27904969/metabolic-responses-and-omics-technologies-for-elucidating-the-effects-of-heat-stress-in-dairy-cows
#20
REVIEW
Li Min, Shengguo Zhao, He Tian, Xu Zhou, Yangdong Zhang, Songli Li, Hongjian Yang, Nan Zheng, Jiaqi Wang
Heat stress (HS) negatively affects various industries that rely on animal husbandry, particularly the dairy industry. A better understanding of metabolic responses in HS dairy cows is necessary to elucidate the physiological mechanisms of HS and offer a new perspective for future research. In this paper, we review the current knowledge of responses of body metabolism (lipid, carbohydrate, and protein), endocrine profiles, and bovine mammary epithelial cells during HS. Furthermore, we summarize the metabolomics and proteomics data that have revealed the metabolite profiles and differentially expressed proteins that are a feature of HS in dairy cows...
November 30, 2016: International Journal of Biometeorology
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