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https://www.readbyqxmd.com/read/28344991/antibody-directed-glucocorticoid-targeting-to-cd163-in-m2-type-macrophages-attenuates-fructose-induced-liver-inflammatory-changes
#1
Pia Svendsen, Jonas H Graversen, Anders Etzerodt, Henrik Hager, Rasmus Røge, Henning Grønbæk, Erik I Christensen, Holger J Møller, Hendrik Vilstrup, Søren K Moestrup
Increased consumption of high-caloric carbohydrates contributes substantially to endemic non-alcoholic fatty liver disease in humans, covering a histological spectrum from fatty liver to steatohepatitis. Hypercaloric intake and lipogenetic effects of fructose and endotoxin-driven activation of liver macrophages are suggested to be essential to disease progression. In the present study, we show that a low dose of an anti-CD163-IgG-dexamethasone conjugate targeting the hemoglobin scavenger receptor CD163 in Kupffer cells and other M2-type macrophages has a profound effect on liver inflammatory changes in rats on a high-fructose diet...
March 17, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28341178/mechanisms-underlying-sodium-nitroprusside-induced-tolerance-in-the-mouse-aorta-role-of-ros-and-cyclooxygenase-derived-prostanoids
#2
Mariana C Diniz, Vania C Olivon, Lívia D Tavares, Janaina A Simplicio, Natália A Gonzaga, Daniele G de Souza, Lusiane M Bendhack, Carlos R Tirapelli, Daniella Bonaventura
AIMS: To determine the role of reactive oxygen species (ROS) on sodium nitroprusside (SNP)-induced tolerance. Additionally, we evaluated the role of ROS on NF-κB activation and pro-inflammatory cytokines production during SNP-induced tolerance. MAIN METHODS: To induce in vitro tolerance, endothelium-intact or -denuded aortic rings isolated from male Balb-c mice were incubated for 15, 30, 45 or 60min with SNP (10nmol/L). KEY FINDINGS: Tolerance to SNP was observed after incubation of endothelium-denuded, but not endothelium-intact aortas for 60min with this inorganic nitrate...
March 21, 2017: Life Sciences
https://www.readbyqxmd.com/read/28338748/role-of-scavenger-receptors-as-damage-associated-molecular-pattern-receptors-in-toll-like-receptor-activation
#3
Kyoko Komai, Takashi Shichita, Minako Ito, Mitsuhiro Kanamori, Shunsuke Chikuma, Akihiko Yoshimura
Damage-associated molecular patterns (DAMPs) have been implicated in sterile inflammation in various tissue injuries. High-mobility group box 1 (HMGB1) is a representative DAMP, and has been shown to transmit signals through receptors for advanced glycation end products (RAGEs) and TLRs, including TLR2 and TLR4. HMGB1 does not, however, bind to TLRs with high affinity; therefore, the mechanism of HMGB1-mediated TLR activation remains unclear. In this study, we found that fluorescently labeled HMGB1 was efficiently internalized into macrophages through class A scavenger receptors...
February 24, 2017: International Immunology
https://www.readbyqxmd.com/read/28337837/sulfated-hyaluronan-attenuates-inflammatory-signaling-pathways-in-macrophages-involving-induction-of-antioxidants
#4
Florent Jouy, Nadine Lohmann, Elke Wandel, Gloria Ruiz-Gómez, M Teresa Pisabarro, Annette G Beck-Sickinger, Matthias Schnabelrauch, Stephanie Moeller, Jan C Simon, Stefan Kalkhof, Martin von Bergen, Sandra Franz
It is well recognized that high molecular weight hyaluronan (H-HA) exerts potent anti-inflammatory effects while its fragmentation into low molecular weight HA (L-HA) is discussed to promote inflammation. Chemical modification of HA with sulfate groups has been shown to foster its anti-inflammatory activity which seems to be maintained in sulfated low molecular weight HA derivatives (sL-HA). However, the molecular mechanisms by which sL-HA produces its anti-inflammatory activity are not understood. In this study, we used global quantitative proteomics combined with targeted analysis of key proteins to characterize the effect of sL-HA on fully differentiated human inflammatory macrophages (iMФ)...
March 24, 2017: Proteomics
https://www.readbyqxmd.com/read/28336528/platelet-cd36-promotes-thrombosis-by-activating-redox-sensor-erk5-in-hyperlipidemic-conditions
#5
Moua Yang, Brian C Cooley, Wei Li, Yiliang Chen, Jeannette Vasquez-Vivar, Na'il O Scoggins, Scott J Cameron, Craig N Morrell, Roy L Silverstein
Atherothrombosis is a process mediated by dysregulated platelet activation that can cause life-threatening complications and is the leading cause of death by cardiovascular disease. Platelet reactivity in hyperlipidemic conditions is enhanced when platelet scavenger receptor CD36 recognizes oxidized lipids in LDL particles, a process which induces an overt prothrombotic phenotype. The mechanisms by which CD36 promotes platelet activation and thrombosis remain incompletely defined. In this study, we identify a mechanism for CD36 to promote thrombosis by increasing activation of MAP kinase ERK5, a protein kinase known to be exquisitely sensitive to redox stress, through a signaling pathway requiring Src kinases, NADPH oxidase, superoxide radical anion and hydrogen peroxide...
March 23, 2017: Blood
https://www.readbyqxmd.com/read/28334203/innate-immune-recognition-and-inflammation-in-neisseria-meningitidis-infection
#6
Kay Johswich
N. meningitidis (Nme) can cause meningitis and sepsis, diseases which are characterized by an overwhelming inflammatory response. Inflammation is triggered by host pattern recognition receptors (PRRs) which are activated by pathogen associated molecular patterns (PAMPs). Nme contains multiple PAMPs including lipooligosaccharide, peptidoglycan, proteins and metabolites. Various classes of PRRs including Toll-like receptors, NOD-like receptors, C-type lectins, scavenger receptors, pentraxins and others are expressed by the host to respond to any given microbe...
March 1, 2017: Pathogens and Disease
https://www.readbyqxmd.com/read/28333093/the-effect-of-regular-intake-of-dry-cured-ham-rich-in-bioactive-peptides-on-inflammation-platelet-and-monocyte-activation-markers-in-humans
#7
Sara María Martínez-Sánchez, Alfredo Minguela, David Prieto-Merino, María Pilar Zafrilla-Rentero, José Abellán-Alemán, Silvia Montoro-García
Background and aims: Dietary studies have shown that active biopeptides provide protective health benefits, although the mediating pathways are somewhat uncertain. To throw light on this situation, we studied the effects of consuming Spanish dry-cured ham on platelet function, monocyte activation markers and the inflammatory status of healthy humans with pre-hypertension. Methods: Thirty-eight healthy volunteers with systolic blood pressure of >125 mmHg were enrolled in a two-arm crossover randomized controlled trial...
March 23, 2017: Nutrients
https://www.readbyqxmd.com/read/28332554/fucoidan-induces-toll-like-receptor-4-regulated-reactive-oxygen-species-and-promotes-endoplasmic-reticulum-stress-mediated-apoptosis-in-lung-cancer
#8
Hsien-Yeh Hsu, Tung-Yi Lin, Mei-Kuang Lu, Pei-Ju Leng, Shu-Ming Tsao, Yu-Chung Wu
Fucoidan, a sulfated polysaccharide extracted from brown algae, exhibits anti-cancer activity. However, the effects and mechanism of fucoidan-induced apoptosis via endoplasmic reticulum (ER) stress is unclear. In this study, we demonstrated that fucoidan prevents tumorigenesis and reduces tumor size in LLC1-xenograft male C57BL/6 mice. Fucoidan induces an ER stress response by activating the PERK-ATF4-CHOP pathway, resulting in apoptotic cell death in vitro and in vivo. Furthermore, ATF4 knockdown abolishes fucoidan-induced CHOP expression and rescues cell viability...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28330995/hepatic-fcrn-regulates-albumin-homeostasis-and-susceptibility-to-liver-injury
#9
Michal Pyzik, Timo Rath, Timothy T Kuo, Sanda Win, Kristi Baker, Jonathan J Hubbard, Rosa Grenha, Amit Gandhi, Thomas D Krämer, Adam R Mezo, Zachary S Taylor, Kevin McDonnell, Vicki Nienaber, Jan Terje Andersen, Atsushi Mizoguchi, Laurence Blumberg, Shalaka Purohit, Susan D Jones, Greg Christianson, Wayne I Lencer, Inger Sandlie, Neil Kaplowitz, Derry C Roopenian, Richard S Blumberg
The neonatal crystallizable fragment receptor (FcRn) is responsible for maintaining the long half-life and high levels of the two most abundant circulating proteins, albumin and IgG. In the latter case, the protective mechanism derives from FcRn binding to IgG in the weakly acidic environment contained within endosomes of hematopoietic and parenchymal cells, whereupon IgG is diverted from degradation in lysosomes and is recycled. The cellular location and mechanism by which FcRn protects albumin are partially understood...
March 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28326017/adiponectin-regulates-the-polarization-and-function-of-microglia-via-ppar-%C3%AE-signaling-under-amyloid-%C3%AE-toxicity
#10
Juhyun Song, Seong-Min Choi, Byeong C Kim
Alzheimer's disease (AD), characterized by the abnormal accumulation of amyloid beta (Aβ), is gradually increasing globally. Given that AD is considered a neuroinflammatory disease, recent studies have focused on the cellular mechanisms in brain inflammatory conditions that underlie AD neuropathology. Microglia are macrophage cells in the central nervous system (CNS) that are activated in response to Aβ condition. The function of microglia contributes to the neuroinflammation in AD brain, suggesting that microglia regulate the production of inflammatory mediators and contribute to the regeneration of damaged tissues...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28323325/the-evolution-of-siderophore-production-as-a-competitive-trait
#11
Rene Niehus, Aurore Picot, Nuno M Oliveira, Sara Mitri, Kevin R Foster
Microbes have the potential to be highly cooperative organisms. The archetype of microbial cooperation is often considered to be the secretion of siderophores, molecules scavenging iron, where cooperation is threatened by "cheater" genotypes that use siderophores without making them. Here we show that this view neglects a key piece of biology: siderophores are imported by specific receptors that constrain their use by competing strains. We study the effect of this specificity in an eco-evolutionary model, in which we vary siderophore sharing among strains, and compare fully shared siderophores with private siderophores...
March 21, 2017: Evolution; International Journal of Organic Evolution
https://www.readbyqxmd.com/read/28323095/megalin-targeted-enhanced-transfection-efficiency-in-cultured-human-hk-2-renal-tubular-proximal-cells-using-aminoglycoside-carboxyalkyl-polyethylenimine-containing-nanoplexes
#12
Fatemeh Oroojalian, Ali Hossein Rezayan, Wayne Thomas Shier, Khalil Abnous, Mohammad Ramezani
Non-viral vectors are of interest as therapeutic gene delivery agents in gene therapy, because they are simple to prepare, easy to modify and have definable safety profiles compared to viral vectors. The potential of gene therapy in the treatment of renal diseases is limited by a lack of effective kidney-targeted gene delivery systems. Aminoglycoside antibiotics gentamicin and neomycin were connected by amide linkages to carboxyl groups on carboxyalkylated-PEI25 (25kDa PEI) or carboxyalkylated-PEI10 (10kDa PEI)...
March 16, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28317919/scavenger-receptor-collectin-placenta-1-is-a-novel-receptor-involved-in-the-uptake-of-myelin-by-phagocytes
#13
Jeroen F J Bogie, Jo Mailleux, Elien Wouters, Winde Jorissen, Elien Grajchen, Jasmine Vanmol, Kristiaan Wouters, Niels Hellings, Jack Van Horsen, Tim Vanmierlo, Jerome J A Hendriks
Myelin-containing macrophages and microglia are the most abundant immune cells in active multiple sclerosis (MS) lesions. Our recent transcriptomic analysis demonstrated that collectin placenta 1 (CL-P1) is one of the most potently induced genes in macrophages after uptake of myelin. CL-P1 is a type II transmembrane protein with both a collagen-like and carbohydrate recognition domain, which plays a key role in host defense. In this study we sought to determine the dynamics of CL-P1 expression on myelin-containing phagocytes and define the role that it plays in MS lesion development...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28315462/implications-of-cerebrovascular-atp-binding-cassette-transporter-g1-abcg1-and-apolipoprotein-m-in-cholesterol-transport-at-the-blood-brain-barrier
#14
Alexandra Carmen Kober, Anil Paul Chirackal Manavalan, Carmen Tam-Amersdorfer, Andreas Holmér, Ahmed Saeed, Elham Fanaee-Danesh, Martina Zandl, Nicole Maria Albrecher, Ingemar Björkhem, Gerhard M Kostner, Björn Dahlbäck, Ute Panzenboeck
Impaired cholesterol/lipoprotein metabolism is linked to neurodegenerative diseases such as Alzheimer's disease (AD). Cerebral cholesterol homeostasis is maintained by the highly efficient blood-brain barrier (BBB) and flux of the oxysterols 24(S)-hydroxycholesterol and 27-hydroxycholesterol, potent liver-X-receptor (LXR) activators. HDL and their apolipoproteins are crucial for cerebral lipid transfer, and loss of ATP binding cassette transporters (ABC)G1 and G4 results in toxic accumulation of oxysterols in the brain...
March 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28315324/nucleolin-protects-macrophages-from-oxldl-induced-foam-cell-formation-through-up-regulating-abca1-expression
#15
Yuanbin Li, Bimei Jiang, Pengfei Liang, Zhongyi Tong, Meidong Liu, Qinglan Lv, Yanjuan Liu, Xuanyou Liu, Yuting Tang, Xianzhong Xiao
Our recent studies have indicated that nucleolin, as a multifunctional RNA-binding protein, exerts protective effects in the myocardial cells and endothelial cells under the condition of oxidative stress. However, the function of nucleolin and its potential mechanism in macrophage-derived foam cell formation remain largely unexplored. ApoE-/- mice were fed with a high-fat diet (HFD) for 10-24 weeks. Protein expression was measured by western blotting or immunofluorescence, and gene expression at the mRNA level was detected by qRT-PCR...
March 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28303896/phospholipid-imprinted-polymers-as-selective-endotoxin-scavengers
#16
Robert Sulc, Gyorgy Szekely, Sudhirkumar Shinde, Celina Wierzbicka, Filipe Vilela, David Bauer, Börje Sellergren
Herein we explore phospholipid imprinting as a means to design receptors for complex glycolipids comprising the toxic lipopolysaccharide endotoxin. A series of polymerizable bis-imidazolium and urea hosts were evaluated as cationic and neutral hosts for phosphates and phosphonates, the latter used as mimics of the phospholipid head groups. The bis-imidazolium hosts interacted with the guests in a cooperative manner leading to the presence of tight and well defined 1:2 ternary complexes. Optimized monomer combinations were subsequently used for imprinting of phosphatidic acid as an endotoxin dummy template...
March 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28301373/rediscovering-scavenger-receptor-type-bi-surprising-new-roles-for-the-hdl-receptor
#17
Menno Hoekstra, Mary Sorci-Thomas
PURPOSE OF REVIEW: Scavenger receptor BI (SR-BI) is classically known for its role in antiatherogenic reverse cholesterol transport as it selectively takes up cholesterol esters from HDL. Here, we have highlighted recent literature that describes novel functions for SR-BI in physiology and disease. RECENT FINDINGS: A large population-based study has revealed that patients heterozygous for the P376L mutant form of SR-BI showed significantly increased levels of plasma HDL-cholesterol and had increased risk of cardiovascular disease, demonstrating that SR-BI in humans is a significant determinant of cardiovascular disease...
March 15, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28298522/scavenger-receptor-marco-orchestrates-early-defenses-and-contributes-to-fungal-containment-during-cryptococcal-infection
#18
Jintao Xu, Adam Flaczyk, Lori M Neal, Zhenzong Fa, Alison J Eastman, Antoni N Malachowski, Daphne Cheng, Bethany B Moore, Jeffrey L Curtis, John J Osterholzer, Michal A Olszewski
The scavenger receptor macrophage receptor with collagenous structure (MARCO) promotes protective innate immunity against bacterial and parasitic infections; however, its role in host immunity against fungal pathogens, including the major human opportunistic fungal pathogen Cryptococcus neoformans, remains unknown. Using a mouse model of C. neoformans infection, we demonstrated that MARCO deficiency leads to impaired fungal control during the afferent phase of cryptococcal infection. Diminished fungal containment in MARCO(-/-) mice was accompanied by impaired recruitment of Ly6C(high) monocytes and monocyte-derived dendritic cells (moDC) and lower moDC costimulatory maturation...
March 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28292946/nox2-dependent-immunosuppression-in-chronic-myelomonocytic-leukemia
#19
Johan Aurelius, Alexander Hallner, Olle Werlenius, Rebecca Riise, Lars Möllgård, Mats Brune, Markus Hansson, Anna Martner, Fredrik B Thorén, Kristoffer Hellstrand
Chronic myelomonocytic leukemia (CMML) is a myeloproliferative and myelodysplastic neoplasm with few treatment options and dismal prognosis. The role of natural killer (NK) cells and other antileukemic lymphocytes in CMML is largely unknown. We aimed to provide insight into the mechanisms of immune evasion in CMML with a focus on immunosuppressive reactive oxygen species (ROS) formed by the myeloid cell NADPH oxidase-2 (NOX2). The dominant population of primary human CMML cells was found to express membrane-bound NOX2 and to release ROS, which, in turn, triggered extensive PARP-1-dependent cell death in cocultured NK cells, CD8(+) T effector memory cells, and CD8(+) T effector cells...
March 14, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28291959/the-opening-of-atp-sensitive-k-channels-protects-h9c2-cardiac-cells-against-the-high-glucose-induced-injury-and-inflammation-by-inhibiting-the-ros-tlr4-necroptosis-pathway
#20
Weijie Liang, Meiji Chen, Dongdan Zheng, Jianhao Li, Mingcai Song, Wenzhu Zhang, Jianqiang Feng, Jun Lan
BACKGROUND/AIMS: Hyperglycemia activates multiple signaling molecules, including reactive oxygen species (ROS), toll-like receptor 4 (TLR4), receptor-interacting protein 3 (RIP3, a kinase promoting necroptosis), which mediate hyperglycemia-induced cardiac injury. This study explored whether inhibition of ROS-TLR4-necroptosis pathway contributed to the protection of ATP-sensitive K+ (KATP) channel opening against high glucose-induced cardiac injury and inflammation. METHODS: H9c2 cardiac cells were treated with 35 mM glucose (HG) to establish a model of HG-induced insults...
February 22, 2017: Cellular Physiology and Biochemistry
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