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cytokines metabolic

Thuy-Truc Ta, Hasan Onur Dikmen, Simone Schilling, Bruno Chausse, Andrea Lewen, Jan-Oliver Hollnagel, Oliver Kann
Type II IFN (IFN-γ) is a proinflammatory T lymphocyte cytokine that serves in priming of microglia-resident CNS macrophages-during the complex microglial activation process under pathological conditions. Priming generally permits an exaggerated microglial response to a secondary inflammatory stimulus. The impact of primed microglia on physiological neuronal function in intact cortical tissue (in situ) is widely unknown, however. We explored the effects of chronic IFN-γ exposure on microglia in hippocampal slice cultures, i...
February 19, 2019: Proceedings of the National Academy of Sciences of the United States of America
Ding-Hui Dai, Izhar Hyder Qazi, Ming-Xia Ran, Kai Liang, Yan Zhang, Ming Zhang, Guang-Bin Zhou, Christiana Angel, Chang-Jun Zeng
Due to lower farrowing rate and reduced litter size with frozen-thawed semen, over 90% of artificial insemination (AI) is conducted using liquid stored boar semen. Although substantial progress has been made towards optimizing the cryopreservation protocols for boar sperm, the influencing factors and underlying mechanisms related to cryoinjury and freeze tolerance of boar sperm remain largely unknown. In this study, we report the differential expression of mRNAs and miRNAs between fresh and frozen-thawed boar sperm using high-throughput RNA sequencing...
February 13, 2019: International Journal of Molecular Sciences
Ufuk Tan Timur, Marjolein Caron, Guus van den Akker, Anna van der Windt, Jenny Visser, Lodewijk van Rhijn, Harrie Weinans, Tim Welting, Pieter Emans, Holger Jahr
During standard expansion culture (i.e., plasma osmolarity, 280 mOsm) human articular chondrocytes dedifferentiate, making them inappropriate for autologous chondrocyte implantation to treat cartilage defects. Increasing the osmolarity of culture media to physiological osmolarity levels of cartilage (i.e., 380 mOsm), increases collagen type II ( COL2A1 ) expression of human articular chondrocytes in vitro , but the underlying molecular mechanism is not fully understood. We hypothesized that TGF-β superfamily signaling may drive expression of COL2A1 under physiological osmolarity culture conditions...
February 13, 2019: International Journal of Molecular Sciences
Taiwo O Elufioye, Solomon Habtemariam
Liver diseases such as hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma are one of the major health challenges in the world and many conditions such as inadequate nutrition, viral infection, ethanol and drug abuse, xenobiotic exposure, and metabolic diseases have been implicated in the development and progression of liver diseases. Several factors including lipid peroxidation, production of reactive oxygen species (ROS), peroxynitrite formation, complement factors and proinflammatory mediators, such as cytokines and chemokines, are involved in hepatic diseases...
February 16, 2019: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Christian Neumann, Jonas Blume, Urmi Roy, Peggy P Teh, Ajithkumar Vasanthakumar, Alexander Beller, Yang Liao, Frederik Heinrich, Teresita L Arenzana, Jason A Hackney, Celine Eidenschenk, Eric J C Gálvez, Christina Stehle, Gitta A Heinz, Patrick Maschmeyer, Tom Sidwell, Yifang Hu, Derk Amsen, Chiara Romagnani, Hyun-Dong Chang, Andrey Kruglov, Mir-Farzin Mashreghi, Wei Shi, Till Strowig, Sascha Rutz, Axel Kallies, Alexander Scheffold
Foxp3+ regulatory T cells (Treg cells) are crucial for the maintenance of immune homeostasis both in lymphoid tissues and in non-lymphoid tissues. Here we demonstrate that the ability of intestinal Treg cells to constrain microbiota-dependent interleukin (IL)-17-producing helper T cell (TH 17 cell) and immunoglobulin A responses critically required expression of the transcription factor c-Maf. The terminal differentiation and function of several intestinal Treg cell populations, including RORγt+ Treg cells and follicular regulatory T cells, were c-Maf dependent...
February 18, 2019: Nature Immunology
Timothy Nacarelli, Lena Lau, Takeshi Fukumoto, Joseph Zundell, Nail Fatkhutdinov, Shuai Wu, Katherine M Aird, Osamu Iwasaki, Andrew V Kossenkov, David Schultz, Ken-Ichi Noma, Joseph A Baur, Zachary Schug, Hsin-Yao Tang, David W Speicher, Gregory David, Rugang Zhang
Cellular senescence is a stable growth arrest that is implicated in tissue ageing and cancer. Senescent cells are characterized by an upregulation of proinflammatory cytokines, which is termed the senescence-associated secretory phenotype (SASP). NAD+ metabolism influences both tissue ageing and cancer. However, the role of NAD+ metabolism in regulating the SASP is poorly understood. Here, we show that nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of the NAD+ salvage pathway, governs the proinflammatory SASP independent of senescence-associated growth arrest...
February 18, 2019: Nature Cell Biology
Pulavendran Sivasami, Nabin Poudel, Maria Cristina Munteanu, Joanna Hudson, Pamela Lovern, Lin Liu, Tim Griffin, Myron E Hinsdale
BACKGROUND/OBJECTIVES: The cellular and extracellular matrix (ECM) interactions that regulate adipose tissue homeostasis are incompletely understood. Proteoglycans (PGs) and their sulfated glycosaminoglycans (GAGs) provide spatial and temporal signals for ECM organization and interactions with resident cells by impacting growth factor and cytokine activity. Therefore, PGs and their GAGs could be significant to adipose tissue homeostasis. The purpose of this study was to determine the role of ECM sulfated GAGs in adipose tissue homeostasis...
February 18, 2019: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Troy D Hubbard, Qing Liu, Iain A Murray, Fangcong Dong, Charles Miller Iii, Phillip B Smith, Krishne Gowda, Jyh Ming Lin, Shantu Amin, Andrew D Patterson, Gary H Perdew
The Aryl hydrocarbon receptor (AHR) is a major regulator of immune function within the gastrointestinal tract. Resident microbiota are capable influencing AHR-dependent signaling pathways via production of an array of bioactive molecules that act as AHR agonists, such as indole or indole-3-aldehyde. Bacteria produce a number of quinoline derivatives, of which some function as quorum-sensing molecules. Thus, we screened relevant hydroxyquinoline derivatives for AHR activity using AHR responsive reporter cell lines...
February 19, 2019: Journal of Proteome Research
Sriram Bandi, Tatyana Tchaikovskaya, Sanjeev Gupta
Endogenous cell signals regulate tissue homeostasis and are significant for directing the fate of stem cells. During liver development, cytokines released from various cell types are critical for stem/progenitor cell differentiation and lineage expansions. To determine mechanisms in these stage-specific lineage interactions, we modeled potential effects of soluble signals derived from immortalized human fetal liver parenchymal cells on stem cells, including embryonic and induced pluripotent stem cells. For identifying lineage conversion and maturation, we utilized conventional assays of cell morphology, gene expression analysis and lineage markers...
January 28, 2019: Differentiation; Research in Biological Diversity
Tyler Etheridge, Shivashankar Damodaran, Adam Schultz, Kyle A Richards, Joseph Gawdzik, Bing Yang, Vincent Cryns, David F Jarrard
Androgen deprivation therapy (ADT) has been the standard of care for the last 75 years in metastatic hormone sensitive prostate cancer (PCa). However, this approach is rarely curative. Recent clinical trials have demonstrated that ADT combined with other agents, notably docetaxel and abiraterone, lead to improved survival. The mechanisms surrounding this improved cancer outcomes are incompletely defined. The response of cancer cells to ADT includes apoptosis and cell death, but a significant fraction remains viable...
January 2019: Asian Journal of Urology
Huadan Xu, Liankun Sun, Yichun He, Xiaofeng Yuan, Junqi Niu, Jing Su, Dong Li
The polarization and function of macrophages play essential roles in controlling immune responses. Interleukin (IL)-33 is a member of the IL-1 family that has been shown to influence macrophage activation and polarization, but the underlying mechanisms are not fully understood. Mitochondrial metabolism has been reported to be a central player in shaping macrophage polarization; previous studies have shown that both aerobic glycolysis and oxidative phosphorylation uniquely regulate the functions of M1 and M2 macrophages...
2019: Frontiers in Immunology
Arianne E Rodriguez, Gregory S Ducker, Leah K Billingham, Carlos A Martinez, Nello Mainolfi, Vipin Suri, Adam Friedman, Mark G Manfredi, Samuel E Weinberg, Joshua D Rabinowitz, Navdeep S Chandel
Serine is a substrate for nucleotide, NADPH, and glutathione (GSH) synthesis. Previous studies in cancer cells and lymphocytes have shown that serine-dependent one-carbon units are necessary for nucleotide production to support proliferation. Presently, it is unknown whether serine metabolism impacts the function of non-proliferative cells, such as inflammatory macrophages. We find that in macrophages, serine is required for optimal lipopolysaccharide (LPS) induction of IL-1β mRNA expression, but not inflammasome activation...
February 7, 2019: Cell Metabolism
Wen Ding, Yuan-Yuan Fan, Cheng Zhang, Lin Fu, Xi Chen, De-Xiang Xu
The farnesoid X receptor (FXR) is a ligand-activated transcription factor that regulates genes involved in bile acid metabolism. Accumulating data demonstrate that FXR has an anti-inflammatory activity. The present study aimed to investigate the effect of obeticholic acid (OCA), a novel synthetic FXR agonist, on D-galactosamine (GalN)/lipopolysaccharide (LPS)-evoked acute liver injury. All mice except controls were intraperitoneally injected with GalN (300mg/kg) plus LPS (2.5μg/kg). Some mice were pretreated with OCA (10mg/kg) 48, 24 and 1h before GalN/LPS...
February 14, 2019: European Journal of Pharmacology
Michal B Juda, Alexandra K Brooks, Albert E Towers, Gregory G Freund, Robert H McCusker, Andrew J Steelman
OBJECTIVE: Viral encephalitis increases the risk for developing seizures and epilepsy. Indoleamine 2,3-dioxygenase 1 (Ido1) is induced by inflammatory cytokines and functions to metabolize tryptophan to kynurenine. Kynurenine can be further metabolized to produce kynurenic acid and the N-methyl-d-aspartate receptor agonist quinolinic acid (QuinA). In the present study, we sought to determine the role of Ido1 in promoting seizures in an animal model of viral encephalitis. METHODS: C57BL/6J and Ido1 knockout mice (Ido1-KO) were infected with Theiler's murine encephalomyelitis virus (TMEV)...
February 15, 2019: Epilepsia
Raquel Guillamat-Prats, Martina Rami, Stephan Herzig, Sabine Steffens
Endocannabinoids are a group of arachidonic acid-derived lipid mediators binding to cannabinoid receptors CB1 and CB2. An overactivity of the endocannabinoid system plays a pathophysiological role in the development of visceral obesity and insulin resistance. Moreover, elevated circulating endocannabinoid levels are also prevalent in atherosclerosis. The pathophysiological increase of endocannabinoid levels is due to an altered expression of endocannabinoid synthesizing and degrading enzymes induced by inflammatory mediators such as cytokines or lipids...
February 15, 2019: Thrombosis and Haemostasis
Jiasheng Wang, Yongxian Hu, Shuye Yang, Guoqin Wei, Xin Zhao, Wenjun Wu, Yanlei Zhang, Yafei Zhang, Donghe Chen, Zhao Wu, Lei Xiao, Alex Hongsheng Chang, He Huang, Kui Zhao
BACKGROUND: CD19-targeting chimeric antigen receptor (CAR) T cell therapy has shown great efficacy in patients with relapsed/refractory non-Hodgkin lymphoma (NHL), but has been associated with serious adverse effects such as cytokine release syndrome (CRS). It has been speculated that NHL baseline disease burden might affect clinical outcome and CRS, but such assumption has not been explored in detail. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG), as measured by FDG PET-CT, are quantitative indicators of baseline tumor burden...
February 12, 2019: Biology of Blood and Marrow Transplantation
Cecilie Bay-Richter, Eskild Petersen, Nico Liebenberg, Betina Elfving, Gregers Wegener
Toxoplasma gondii (TOX) is an intracellular parasite which infects warm-blooded animals including humans. An increasing number of clinical studies now hypothesize that latent toxoplasmosis may be a risk factor for the development of psychiatric disease. For depression, the results have been varied and we speculate that genetic background is important for the response to latent toxoplasmosis. The main objective of this study was to elucidate gene - environment interactions in the behavioural response to TOX infection by use of genetically vulnerable animals (Flinders sensitive line, FSL) compared to control animals (Flinders resistant line, FRL)...
February 12, 2019: Behavioural Brain Research
Thais de Castro Barbosa, Petter S Alm, Anna Krook, Romain Barrès, Juleen R Zierath
Paternal preconceptional high-fat diet (HFD) alters whole-body glucose and energy homeostasis over several generations, which may be mediated by altered transcriptomic profiles of metabolic organs. We investigated the effect of paternal HFD on the hepatic transcriptomic and metabolic signatures of female grand-offspring. Paternal HFD strongly impacted the liver transcriptome of the second-generation offspring. Gene set enrichment analysis (GSEA) revealed grandpaternal-HFD altered the TNF-α signaling via NFκB pathway, independent of the grand-offspring's diet...
February 15, 2019: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Kenneth N Maclean, Hua Jiang, Whitney N Phinney, Amy K Keating, K Joseph Hurt, Sally P Stabler
Classical cystathionine β-synthase-deficient homocystinuria (HCU) is a life-threatening inborn error of sulfur metabolism. Treatment for pyridoxine-nonresponsive HCU involves lowering homocysteine (Hcy) with a methionine (Met)-restricted diet and betaine supplementation. Betaine treatment efficacy diminishes significantly over time due to impairment of betaine-Hcy S-methyltransferase (BHMT) function. Little is known regarding the regulation of BHMT in HCU. Using a betaine-responsive preclinical mouse model of HCU, we observed that this condition induces a 75% repression of BHMT mRNA, protein and enzyme activity, and significant depletion of hepatic betaine levels...
February 15, 2019: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
N Rafiee Tari, E Arranz, M Corredig
An increasing body of evidence demonstrates that differences in protein composition in the food matrix can significantly affect its biological functionality. The present research hypothesized that a matrix containing the same level of dairy protein, but with different composition, even when showing similar properties during digestion, may have a different biological functionality. To test this hypothesis, three matrices, containing 2.8% protein and similar amounts of fat and solid were prepared, either with 100% whey proteins, or with a ratio of caseins to whey protein of 40 : 60, but differing in β-casein ratio...
February 15, 2019: Food & Function
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