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Immune glycolysis

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https://www.readbyqxmd.com/read/28069950/chronic-innate-immune-activation-of-tbk1-suppresses-mtorc1-activity-and-dysregulates-cellular-metabolism
#1
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 9, 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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27918097/sugars-and-fat-a-healthy-way-to-generate-functional-regulatory-t-cells
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/27903739/homocysteine-activates-b-cells-via-regulating-pkm2-dependent-metabolic-reprogramming
#12
Jiacheng Deng, Silin Lü, Huiying Liu, Bo Liu, Changtao Jiang, Qingbo Xu, Juan Feng, Xian Wang
The overactivation of immune cells plays an important role in the pathogenesis of hyperhomocysteinemia (HHcy)-accelerated atherosclerosis. Homocysteine (Hcy) activates B cell proliferation and Ab secretion; however, the underlying mechanisms for these effects remain largely unknown. Metabolic reprogramming is critical for lymphocyte activation and effector function. In this study, we showed that Hcy-activated B cells displayed an increase in both oxidative phosphorylation and glycolysis, with a tendency to shift toward the latter, as well as an accumulation of intermediates in the pentose phosphate pathway, to provide energy and biosynthetic substrates for cell growth and function...
January 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27898346/amp-kinase-promotes-bcl6-expression-in-both-mouse-and-human-t-cells
#13
Markus M Xie, Tohti Amet, Hong Liu, Qigui Yu, Alexander L Dent
The transcription factor Bcl6 is a master regulator of follicular helper T (TFH) cells, and understanding the signaling pathway that induces Bcl6 and TFH cell differentiation is therefore critical. IL-2 produced during T cell activation inhibits Bcl6 expression but how TFH cells evade IL-2 inhibition is not completely understood. Here we show that Bcl6 is highly up-regulated in activated CD4 T cells following glucose deprivation (GD), and this pathway is insensitive to inhibition by IL-2. Similar to GD, the glucose analog 2-deoxyglucose (2DG) inhibits glycolysis, and 2DG induced Bcl6 expression in activated CD4 T cells...
January 2017: Molecular Immunology
https://www.readbyqxmd.com/read/27884183/rna-sequencing-for-profiling-goat-milk-transcriptome-in-colostrum-and-mature-milk
#14
Alessandra Crisà, Fabrizio Ferrè, Giovanni Chillemi, Bianca Moioli
BACKGROUND: In this work we aimed at sequencing and assembling the goat milk transcriptome corresponding at colostrum and 120 days of lactation. To reconstruct transcripts we used both the genome as reference, and a de novo assembly approach. Additionally, we aimed at identifying the differentially expressed genes (DEGs) between the two lactation stages and at analyzing the expression of genes involved in oligosaccharides metabolism. RESULTS: A total of 44,635 different transcripts, organized in 33,757 tentative genes, were obtained using the goat genome as reference...
November 25, 2016: BMC Veterinary Research
https://www.readbyqxmd.com/read/27883186/lactate-at-the-crossroads-of-metabolism-inflammation-and-autoimmunity
#15
Valentina Pucino, Michele Bombardieri, Costantino Pitzalis, Claudio Mauro
For a long time after its discovery at the beginning of the 20th century, lactate was considered a waste product of cellular metabolism. Starting in the early '90s, however, lactate has begun to be recognized as an active molecule capable of modulating the immune response. Inflammatory sites, including in rheumatoid arthritis (RA) synovitis, are characterized by the accumulation of lactate, which is partly responsible for the establishment of an acidic environment. We have recently reported that T cells sense lactate via the expression of specific transporters, leading to inhibition of their motility...
January 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/27883071/mint3-apba3-depletion-ameliorates-severe-murine-influenza-pneumonia-and-macrophage-cytokine-production-in-response-to-the-influenza-virus
#16
Takayuki Uematsu, Tomoko Fujita, Hiroki J Nakaoka, Toshiro Hara, Noritada Kobayashi, Yoshinori Murakami, Motoharu Seiki, Takeharu Sakamoto
Influenza virus (IFV) infection is a common cause of severe pneumonia. Studies have suggested that excessive activation of the host immune system including macrophages is responsible for the severe pathologies mediated by IFV infection. Here, we focused on the X11 protein family member Mint3/Apba3, known to promote ATP production via glycolysis by activating hypoxia inducible factor-1 (HIF-1) in macrophages, and examined its roles in lung pathogenesis and anti-viral defence upon IFV infection. Mint3-deficient mice exhibited improved influenza pneumonia with reduced inflammatory cytokines/chemokine levels and neutrophil infiltration in the IFV-infected lungs without alteration in viral burden, type-I interferon production, or acquired immunity...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27866838/glutaminolysis-and-fumarate-accumulation-integrate-immunometabolic-and-epigenetic-programs-in-trained-immunity
#17
Rob J W Arts, Boris Novakovic, Rob Ter Horst, Agostinho Carvalho, Siroon Bekkering, Ekta Lachmandas, Fernando Rodrigues, Ricardo Silvestre, Shih-Chin Cheng, Shuang-Yin Wang, Ehsan Habibi, Luís G Gonçalves, Inês Mesquita, Cristina Cunha, Arjan van Laarhoven, Frank L van de Veerdonk, David L Williams, Jos W M van der Meer, Colin Logie, Luke A O'Neill, Charles A Dinarello, Niels P Riksen, Reinout van Crevel, Clary Clish, Richard A Notebaart, Leo A B Joosten, Hendrik G Stunnenberg, Ramnik J Xavier, Mihai G Netea
Induction of trained immunity (innate immune memory) is mediated by activation of immune and metabolic pathways that result in epigenetic rewiring of cellular functional programs. Through network-level integration of transcriptomics and metabolomics data, we identify glycolysis, glutaminolysis, and the cholesterol synthesis pathway as indispensable for the induction of trained immunity by β-glucan in monocytes. Accumulation of fumarate, due to glutamine replenishment of the TCA cycle, integrates immune and metabolic circuits to induce monocyte epigenetic reprogramming by inhibiting KDM5 histone demethylases...
December 13, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27856732/trypanosoma-brucei-metabolite-indolepyruvate-decreases-hif-1%C3%AE-and-glycolysis-in-macrophages-as-a-mechanism-of-innate-immune-evasion
#18
Anne F McGettrick, Sarah E Corcoran, Paul J G Barry, Jennifer McFarland, Cécile Crès, Anne M Curtis, Edward Franklin, Sinéad C Corr, K Hun Mok, Eoin P Cummins, Cormac T Taylor, Luke A J O'Neill, Derek P Nolan
The parasite Trypanasoma brucei causes African trypanosomiasis, known as sleeping sickness in humans and nagana in domestic animals. These diseases are a major burden in the 36 sub-Saharan African countries where the tsetse fly vector is endemic. Untreated trypanosomiasis is fatal and the current treatments are stage-dependent and can be problematic during the meningoencephalitic stage, where no new therapies have been developed in recent years and the current drugs have a low therapeutic index. There is a need for more effective treatments and a better understanding of how these parasites evade the host immune response will help in this regard...
November 29, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27852741/sensitivity-to-restimulation-induced-cell-death-is-linked-to-glycolytic-metabolism-in-human-t-cells
#19
Sasha E Larsen, Abegail Bilenkin, Tatiana N Tarasenko, Swadhinya Arjunaraja, Jeffrey R Stinson, Peter J McGuire, Andrew L Snow
Restimulation-induced cell death (RICD) regulates immune responses by restraining effector T cell expansion and limiting nonspecific damage to the host. RICD is triggered by re-engagement of the TCR on a cycling effector T cell, resulting in apoptosis. It remains unclear how RICD sensitivity is calibrated in T cells derived from different individuals or subsets. In this study we show that aerobic glycolysis strongly correlates with RICD sensitivity in human CD8(+) effector T cells. Reducing glycolytic activity or glucose availability rendered effector T cells significantly less sensitive to RICD...
January 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27832958/hypoxia-inducible-factor-prolyl-4-hydroxylase-inhibition-in-cardiometabolic-diseases
#20
REVIEW
Peppi Koivunen, Raisa Serpi, Elitsa Y Dimova
Hypoxia-inducible factor prolyl 4-hydroxylases (HIF-P4Hs, also called PHDs and EglNs) are enzymes that act as cellular oxygen sensors. They are the main downregulators of the hypoxia-inducible factor (HIF). HIF-P4Hs can be targeted with small molecule inhibitors, which stabilize HIF under normoxia and initiate the hypoxia response. Such inhibitors are in phase 2 and 3 clinical trials for the treatment of anemia due to their ability to induce erythropoietin and iron metabolism genes. Recent data suggest that HIF-P4H inhibition has a therapeutic role beyond anemia in cardiac ischemia, obesity and metabolic dysfunction, and atherosclerosis...
December 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
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