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https://www.readbyqxmd.com/read/28708972/uv-irradiation-of-skin-enhances-glycolytic-flux-and-reduces-migration-capabilities-in-bone-marrow-differentiated-dendritic-cells
#1
Terence A McGonigle, Kevin N Keane, Simon Ghaly, Kim W Carter, Denise Anderson, Naomi M Scott, Helen S Goodridge, Amy Dwyer, Eloise Greenland, Fiona J Pixley, Philip Newsholme, Prue H Hart
A systemic immunosuppression follows UV irradiation of the skin of humans and mice. In this study, dendritic cells (DCs) differentiating from the bone marrow of UV-irradiated mice had a reduced ability to migrate toward the chemokine (C-C motif) ligand 21. Fewer DCs also accumulated in the peritoneal cavity of UV-chimeric mice (ie, mice transplanted with bone marrow from UV-irradiated mice) after injection of an inflammatory stimulus into that site. We hypothesized that different metabolic states underpin altered DC motility...
July 11, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28705991/oxygen-metabolism-and-innate-immune-responses-in-the-gut
#2
Sean Patrick Colgan, Eric L Campbell
Epithelial cells of the mucosa provide a first line of protection against the inappropriate flux of antigens from the outside world. In the gastrointestinal (GI) tract, this barrier is provided at a number of levels, including mucus production, epithelial junctional complexes and the production of antimicrobial molecules. In recent years, it is better appreciated that tissue oxygen metabolism is key to homeostasis in the mucosa. The intestine, for example, maintains a low baseline pO2 levels due to counter-current blood flow and the presence of large numbers of bacteria...
July 13, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28702931/autophagy-induced-by-bovine-viral-diarrhea-virus-infection-counteracts-apoptosis-and-innate-immune-activation
#3
Yulong Zhou, Yachao Ren, Yanlong Cong, Yu Mu, Renfu Yin, Zhuang Ding
Bovine viral diarrhea virus (BVDV) is an important pathogen of cattle that plays a complex role in disease. There are two biotypes of BVDV: non-cytopathic (NCP) and cytopathic (CP). One strategy that has been used to treat or prevent virus-associated diseases is the modulation of autophagy, which is used by the innate immune system to defend against viral infection; however, at present, the interplay between autophagy and BVDV remains unclear. Madin-Darby bovine kidney cells stably expressing microtubule-associated protein 1 light chain 3B (LC3B) with green fluorescent protein (GFP) (GFP-LC3-MDBK cells) and autophagy-deficient MDBKs (shBCN1-MDBK cells) were constructed...
July 12, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28691995/the-role-of-psychological-stress-on-heart-autophagy-in-mice-with-heart-failure
#4
Xiao-Ting Lu, Xiao-Qiong Liu, Bo Wang, Yuan-Yuan Sun, Rui-Xue Yang, Yi-Fan Xing, Ping Sun, Ying-Bin Wang, Yu-Xia Zhao
OBJECTIVE: Psychological stress in chronic heart failure (CHF) is associated with systemic neurohormonal and immune system responses and increased mortality. Autophagy refers to the biological process of degradation and recycling of dysfunctional cellular components. We investigated the role of psychological stress on autophagy function in CHF mice. RESULTS: A one-week stress exposure significantly increased serum levels of corticosterone and Ang II (P= .000), increased levels of oxidative stress, induced overt heart failure, and increased mortality (P =...
July 7, 2017: Psychosomatic Medicine
https://www.readbyqxmd.com/read/28690610/toll-like-receptor-4-inhibition-improves-oxidative-stress-and-mitochondrial-health-in-isoproterenol-induced-cardiac-hypertrophy-in-rats
#5
Parmeshwar B Katare, Pankaj K Bagul, Amit K Dinda, Sanjay K Banerjee
BACKGROUND: Inflammation remains a crucial factor for progression of cardiac diseases and cardiac hypertrophy remains an important cause of cardiac failure over all age groups. As a key regulator of inflammation, toll-like receptor 4 (TLR4) plays an important role in pathogenesis of cardiac diseases. Being an important regulator of innate immunity, the precise pathway of TLR4-mediated cardiac complications is yet to be established. Therefore, the primary objective of the present study was to find the role of TLR4 in cardiac hypertrophy and the molecular mechanism thereof...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28690139/4-aroyl-3-hydroxy-5-phenyl-1h-pyrrol-2-5h-ones-as-n-formyl-peptide-receptor-1-fpr1-antagonists
#6
Liliya N Kirpotina, Igor A Schepetkin, Andrei I Khlebnikov, Olga I Ruban, Yunjun Ge, Richard D Ye, Douglas J Kominsky, Mark T Quinn
Formyl peptide receptors (FPRs) are expressed on a variety of leukocytes and play important roles in inflammation. Thus, FPR antagonists may represent novel therapeutics for modulating innate immunity and treating inflammatory diseases. Previously, 1H-pyrrol-2(5H)-ones were reported to be potent and competitive FPR1 antagonists. In the present studies, 42 additional 1H-pyrrol-2(5H)-one analogs were evaluated for FPR1 antagonist activity. We identified a number of novel competitive FPR1 antagonists that inhibited N-formylmethionyl-leucyl-phenylalanine (fMLF)-induced intracellular Ca(2+) mobilization in FPR1-transfected HL60 cells and effectively competed with WKYMVm-FITC for binding to FPR1 in FPR1-transfected RBL cells...
July 6, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28685841/krebs-cycle-rewired-for-macrophage-and-dendritic-cell-effector-functions
#7
REVIEW
D G Ryan, L A O'Neill
The Krebs cycle is an amphibolic pathway operating in the mitochondrial matrix of all eukaryotic organisms. In response to pro-inflammatory stimuli, macrophages and dendritic cells undergo profound metabolic remodelling to support the biosynthetic and bioenergetic requirements of the cell. Recently it has been discovered that this metabolic shift also involves the rewiring of the Krebs cycle to regulate cellular metabolic flux and the accumulation of Krebs cycle intermediates, notably, citrate, succinate and fumarate...
July 7, 2017: FEBS Letters
https://www.readbyqxmd.com/read/28676351/bidirectional-brain-gut-interactions-and-chronic-pathological-changes-after-traumatic-brain-injury-in-mice
#8
Elise L Ma, Allen D Smith, Neemesh Desai, Lumei Cheung, Marie Hanscom, Bogdan A Stoica, David J Loane, Terez Shea-Donohue, Alan I Faden
OBJECTIVES: Traumatic brain injury (TBI) has complex effects on the gastrointestinal tract that are associated with TBI-related morbidity and mortality. We examined changes in mucosal barrier properties and enteric glial cell response in the gut after experimental TBI in mice, as well as effects of the enteric pathogen Citrobacter rodentium (Cr) on both gut and brain after injury. METHODS: Moderate-level TBI was induced in C57BL/6 mice by controlled cortical impact (CCI)...
July 1, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28663343/fine-mapping-transcriptome-analysis-and-marker-development-for-y2-the-gene-that-conditions-beta-carotene-accumulation-in-carrot-daucus-carota-l
#9
Shelby Ellison, Douglas Senalik, Hamed Bostan, Massimo Iorizzo, Philipp Simon
Domesticated carrots, Daucus carota subsp. sativus, are the richest source of beta-carotene in the US diet, which when consumed is converted into vitamin A, an essential component of eye health and immunity. The Y2 locus plays a significant role in beta-carotene accumulation in carrot roots, but a candidate gene has not been identified. To advance our understanding of this locus, the genetic basis of beta-carotene accumulation was explored by utilizing an advanced mapping population, transcriptome analysis, and nucleotide diversity in diverse carrot accessions with varying levels of beta-carotene...
June 29, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28647573/focal-adhesion-kinase-signaling-regulates-anti-inflammatory-function-of-bone-marrow-mesenchymal-stromal-cells-induced-by-biomechanical-force
#10
Hyun Jung Lee, Miguel F Diaz, Adesuwa Ewere, Scott D Olson, Charles S Cox, Pamela L Wenzel
Mesenchymal stromal cells (MSCs) have tremendous potential for use in regenerative medicine due to their multipotency and immune cell regulatory functions. Biomimetic physical forces have been shown to direct differentiation and maturation of MSCs in tissue engineering applications; however, the effect of force on immunomodulatory activity of MSCs has been largely overlooked. Here we show in human bone marrow-derived MSCs that wall shear stress (WSS) equivalent to the fluid frictional force present in the adult arterial vasculature significantly enhances expression of four genes that mediate MSC immune regulatory function, PTGS2, HMOX1, IL1RN, and TNFAIP6...
June 21, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28615128/17%C3%AE-estradiol-and-progesterone-decrease-mdp-induced-nod2-expression-in-bovine-mammary-epithelial-cells
#11
Dan-Dan Xu, Gang Wang, Xian-Jing He, Jian-Fa Wang, Bin Yang, Zhi-Peng Sun, Dong-Bo Sun, Qian-Yu He, Xu Zhang, Rui Wu
During the periparturient period, many neuroendocrine changes develop in cows. Periparturient hormone fluxes may adversely affect mammary gland immunity and mastitis susceptibility. 17β-Estradiol (E2) and progesterone (P4) have been reported to function on immune regulation, and their concentration fluctuates dramatically during the perinatal period. Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) mediate numerous aspects of innate immunity in humans and experimental animals. This study aimed to explore the effects of E2 and P4 on NOD2 expression in bovine mammary epithelial cells (BMECs)...
June 2017: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/28611773/fatty-acid-oxidation-compensates-for-lipopolysaccharide-induced-warburg-effect-in-glucose-deprived-monocytes
#12
Nora Raulien, Kathleen Friedrich, Sarah Strobel, Stefan Rubner, Sven Baumann, Martin von Bergen, Antje Körner, Martin Krueger, Manuela Rossol, Ulf Wagner
Monocytes enter sites of microbial or sterile inflammation as the first line of defense of the immune system and initiate pro-inflammatory effector mechanisms. We show that activation with bacterial lipopolysaccharide (LPS) induces them to undergo a metabolic shift toward aerobic glycolysis, similar to the Warburg effect observed in cancer cells. At sites of inflammation, however, glucose concentrations are often drastically decreased, which prompted us to study monocyte function under conditions of glucose deprivation and abrogated Warburg effect...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28603414/iron-oxide-nanoparticles-and-induced-autophagy-in-human-monocytes
#13
QiHong Wu, RongRong Jin, Ting Feng, Li Liu, Li Yang, YuHong Tao, James M Anderson, Hua Ai, Hong Li
Superparamagnetic iron oxide nanoparticles have been widely used in biomedical applications, but understanding of their interactions with the biological immune system is relatively limited. This work is focused on dextran-coated iron oxide nanoparticles and their induced autophagy in human monocytes. We found that these nanoparticles can be taken up by human monocytes, followed by localization within vesicles or free in cytoplasm. Autophagosome formation was observed with increased expression of LC3II protein, the specific marker of autophagy...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28596293/the-uncoupling-of-autophagy-and-zinc-homeostasis-in-airway-epithelial-cells-as-a-fundamental-contributor-to-copd
#14
Eugene Roscioli, Hai Bac Tran, Hubertus Jersmann, Phan Tien Nguyen, Emily Hopkins, Susan Elizabeth Lester, Nigel Farrow, Peter D Zalewski, Paul N Reynolds, Sandra Hodge
The proper regulation of Zinc (Zn) trafficking proteins and the cellular distribution of Zn is critical for the maintenance of autophagic processes. However, there have been no studies which have examined Zn dyshomeostasis and the disease-related modulation of autophagy observed in the airways afflicted with COPD. We hypothesized that dysregulated autophagy in airway epithelial cells (AEC) is related to Zn dysregulation in cigarette smoke (CS)-induced COPD. We applied a human ex vivo air-liquid interface model, a murine model of smoke-exposure, and human lung tissues, and investigated Zn, ZIP1 and ZIP2 Zn-influx proteins, autophagy (Microtubule-associated 1A/1B-light chain-3 (LC3), Beclin-1), autophagic flux (Sequestosome), apoptosis (Bcl2; X-Linked Inhibitor of Apoptosis (XIAP), Poly (ADP)-ribose Polymerase (PARP)), and inflammation (TSLP, RANTES, and IL-1β)...
June 8, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28592540/covalent-linkage-of-hiv-1-trimers-to-synthetic-liposomes-elicits-improved-b-cell-and-antibody-responses
#15
Shridhar Bale, Geraldine Goebrecht, Armando Stano, Richard Wilson, Takayuki Ota, Karen Tran, Jidnyasa Ingale, Michael B Zwick, Richard T Wyatt
We have demonstrated that a liposomal array of well-ordered trimers enhances B cell activation, germinal center formation and the elicitation of tier-2 autologous neutralizing antibodies. Previously, we coupled well-ordered cleavage-independent NFL trimer via their C-terminal poly-histidine tails to nickel-lipids integrated into the lipid bilayer. Despite favorable in vivo effects, concern remains over the potentially longer term in vivo instability of non-covalent linkage of the trimers to the liposomes. Accordingly, we tested both cobalt coupling and covalent linkage of the trimers to the liposomes by reengineering the poly-histidine tail to include a free cysteine on each protomer of model BG505 NFL trimers to allow covalent linkage...
June 7, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28580850/-advances-in-the-pathogenesis-of-non-alcoholic-fatty-liver-disease
#16
Alajos Pár, Gabriella Pár
Non alcoholic fatty liver disease is the hepatic manifestation of metabolic syndrome, and the most common liver disease. Its more aggressive form is the non alcoholic steatohepatitis. Multiple genetic and environmental factors lead to the accumulation of triglicerides and the inflammatory cascade. High fat diet, obesity, adipocyte dysfunction with cytokine production, insulin resistance and increased lipolysis with free fatty acid flux into the liver - all are the drivers of liver cell injury. Activation of inflammasome by damage- or pathogen-associated molecular patterns results in "steril inflammation" and immune response, while the hepatic stellate cells and progenitor cells lead to fibrogenesis...
June 2017: Orvosi Hetilap
https://www.readbyqxmd.com/read/28575583/the-critical-role-played-by-endotoxin-induced-liver-autophagy-in-the-maintenance-of-lipid-metabolism-during-sepsis
#17
Ki Wung Chung, Kyung Mok Kim, Yeon Ja Choi, Hye Jin An, Bonggi Lee, Dae Hyun Kim, Eun Kyeong Lee, Eunok Im, Jaewon Lee, Dong Soon Im, Byung Pal Yu, Hae Young Chung
Macroautophagy/autophagy is a central mechanism by which cells maintain integrity and homeostasis, and endotoxin-induced autophagy plays important roles in innate immunity. Although TLR4 stimulation mediated by lipopolysaccharide (LPS) also upregulates autophagy in hepatocytes and liver, its physiological role remains elusive. The objective of this study was to determine the role of LPS-induced autophagy in the regulation of liver lipid metabolism. LPS treatment (5 mg/kg) increased autophagy, as detected by LC3 conversion and transmission electron microscopy (TEM) analysis in C57BL6 mouse livers...
June 2, 2017: Autophagy
https://www.readbyqxmd.com/read/28555747/liver-x-receptors-link-lipid-metabolism-and-inflammation
#18
REVIEW
Ira G Schulman
The response of immune cells to pathogens is often associated with changes in the flux through basic metabolic pathways. Indeed, in many cases changes in metabolism appear to be necessary for a robust immune response. The Liver X receptors (LXRs) are members of the nuclear hormone receptor superfamily that regulate gene networks controlling cholesterol and lipid metabolism. In immune cells, particularly in macrophages, LXRs also inhibit pro-inflammatory gene expression. This Review will highlight recent studies that connect LXR-dependent control of lipid metabolism to regulation of the immune response...
May 27, 2017: FEBS Letters
https://www.readbyqxmd.com/read/28542477/mycobacterium-tuberculosis-arrests-host-cycle-at-the-g1-s-transition-to-establish-long-term-infection
#19
Bridgette M Cumming, Md Aejazur Rahman, Dirk A Lamprecht, Kyle H Rohde, Vikram Saini, John H Adamson, David G Russell, Adrie J C Steyn
Signals modulating the production of Mycobacterium tuberculosis (Mtb) virulence factors essential for establishing long-term persistent infection are unknown. The WhiB3 redox regulator is known to regulate the production of Mtb virulence factors, however the mechanisms of this modulation are unknown. To advance our understanding of the mechanisms involved in WhiB3 regulation, we performed Mtb in vitro, intraphagosomal and infected host expression analyses. Our Mtb expression analyses in conjunction with extracellular flux analyses demonstrated that WhiB3 maintains bioenergetic homeostasis in response to available carbon sources found in vivo to establish Mtb infection...
May 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28536183/the-nlrp3-inflammasome-contributes-to-sarcopenia-and-lower-muscle-glycolytic-potential-in-old-mice
#20
Marin Jane McBride, Kevin P Foley, Donna M D'souza, Yujin E Li, Trevor C Lau, Thomas J Hawke, Jonathan D Schertzer
The mechanisms underpinning decreased skeletal muscle strength and slowing of movement during aging are ill-defined. "Inflammaging" - increased inflammation with advancing age - may contribute to aspects of sarcopenia, but little is known about the participatory immune components. We discovered that aging was associated with increased caspase-1 activity in mouse skeletal muscle. We hypothesized that the caspase-1 containing NLRP3 inflammasome contributes to sarcopenia in mice. Male C57BL/6J wild type (WT) and NLRP3(-/-) mice were aged to 10 months (adult) and 24 months (old)...
May 23, 2017: American Journal of Physiology. Endocrinology and Metabolism
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