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https://www.readbyqxmd.com/read/28603491/nosh-nbp-a-novel-nitric-oxide-and-hydrogen-sulfide-releasing-hybrid-attenuates-ischemic-stroke-induced-neuroinflammatory-injury-by-modulating-microglia-polarization
#1
Jing Ji, Pengjun Xiang, Tingting Li, Li Lan, Xiaole Xu, Guo Lu, Hui Ji, Yihua Zhang, Yunman Li
NOSH-NBP, a novel nitric oxide (NO) and hydrogen sulfide (H2S)-releasing hybrid, protects brain from ischemic stroke. This study mainly aimed to investigate the therapeutic effect of NOSH-NBP on ischemic stroke and the underlying mechanisms. In vivo, transient middle cerebral artery occlusion (tMCAO) was performed in C57BL/6 mice, with NO-NBP and H2S-NBP as controls. NO and H2S scavengers, carboxy-PTIO and BSS, respectively, were used to quench NO and H2S of NOSH-NBP. In vitro, BV2 microglia/BMDM were induced to the M1/2 phenotype, and conditioned medium (CM) experiments in BV2 microglia, neurons and b...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28596294/the-metalloproteinase-adam8-promotes-leukocyte-recruitment-in-vitro-and-in-acute-lung-inflammation
#2
Daniela Dreymueller, Jessica Pruessmeyer, Julian Schumacher, Sandra Fellendorf, Franz Martin Hess, Anke Seifert, Aaron Babendreyer, Joerg Walter Bartsch, Andreas Ludwig
Alveolar leukocyte recruitment is a hallmark of acute lung inflammation and involves transmigration of leukocytes through endothelial and epithelial layers. The disintegrin and metalloproteinase (ADAM) 8 is expressed on human isolated leukocytic cells and can be further upregulated on cultured endothelial and epithelial cells by proinflammatory cytokines. By shRNA mediated knockdown we show that leukocytic ADAM8 is required on monocytic THP-1 cells for chemokine-induced chemotaxis as well as transendothelial and transepithelial migration...
June 8, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28557543/impaired-mitochondrial-microbicidal-responses-in-chronic-obstructive-pulmonary-disease-macrophages
#3
Martin A Bewley, Julie A Preston, Mohammed Mohasin, Helen M Marriott, Richard C Budd, Julie Swales, Paul Collini, David R Greaves, Ruth W Craig, Christopher E Brightling, Louise E Donnelly, Peter J Barnes, Dave Singh, Steven D Shapiro, Moira K B Whyte, David H Dockrell
RATIONALE: Chronic obstructive pulmonary disease (COPD) is characterized by impaired clearance of pulmonary bacteria. OBJECTIVES: The effect of COPD on alveolar macrophage (AM) microbicidal responses was investigated. METHODS: Alveolar macrophages (AMs) were obtained from bronchoalveolar lavage from healthy donors or COPD patients and challenged with opsonized serotype 14 Streptococcus pneumoniae. Cells were assessed for apoptosis, bactericidal activity and mitochondrial reactive oxygen species (mROS) production...
May 30, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28367448/differential-s1p-receptor-profiles-on-m1-and-m2-polarized-macrophages-affect-macrophage-cytokine-production-and-migration
#4
Jan Müller, Wolfram von Bernstorff, Claus-Dieter Heidecke, Tobias Schulze
Introduction. Macrophages are key players in complex biological processes. In response to environmental signals, macrophages undergo polarization towards a proinflammatory (M1) or anti-inflammatory (M2) phenotype. Sphingosine 1-phosphate (S1P) is a bioactive lysophospholipid that acts via 5 G-protein coupled receptors (S1P1-5) in order to influence a broad spectrum of biological processes. This study assesses S1P receptor expression on macrophages before and after M1 and M2 polarization and performs a comparative analysis of S1P signalling in the two activational states of macrophages...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28340575/nox2-deficiency-alters-macrophage-phenotype-through-an-il-10-stat3-dependent-mechanism-implications-for-traumatic-brain-injury
#5
James P Barrett, Rebecca J Henry, Sonia Villapol, Bogdan A Stoica, Alok Kumar, Mark P Burns, Alan I Faden, David J Loane
BACKGROUND: NADPH oxidase (NOX2) is an enzyme system that generates reactive oxygen species (ROS) in microglia and macrophages. Excessive ROS production is linked with neuroinflammation and chronic neurodegeneration following traumatic brain injury (TBI). Redox signaling regulates macrophage/microglial phenotypic responses (pro-inflammatory versus anti-inflammatory), and NOX2 inhibition following moderate-to-severe TBI markedly reduces pro-inflammatory activation of macrophages/microglia resulting in concomitant increases in anti-inflammatory responses...
March 24, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28278296/robust-growth-of-avirulent-phase-ii-coxiella-burnetii-in-bone-marrow-derived-murine-macrophages
#6
Diane C Cockrell, Carrie M Long, Shelly J Robertson, Jeffrey G Shannon, Heather E Miller, Lara Myers, Charles L Larson, Tregei Starr, Paul A Beare, Robert A Heinzen
Published data show that murine bone marrow-derived macrophages (BMDM) restrict growth of avirulent phase II, but not virulent phase I, Coxiella burnetii. Growth restriction of phase II bacteria is thought to result from potentiated recognition of pathogen-associated molecular patterns, which leads to production of inhibitory effector molecules. Past studies have used conditioned medium from L-929 murine fibroblasts as a source of macrophage-colony stimulating factor (M-CSF) to promote differentiation of bone marrow-derived myeloid precursors into macrophages...
2017: PloS One
https://www.readbyqxmd.com/read/28223293/loss-of-macrophage-fatty-acid-oxidation-does-not-potentiate-systemic-metabolic-dysfunction
#7
Elsie Gonzalez-Hurtado, Jieun Lee, Joseph Choi, Ebru S Selen Alpergin, Samuel L Collins, Maureen R Horton, Michael J Wolfgang
Fatty acid oxidation in macrophages has been suggested to play a causative role in high-fat diet-induced metabolic dysfunction, particularly in the etiology of adipose-driven insulin resistance. To understand the contribution of macrophage fatty acid oxidation directly to metabolic dysfunction in high-fat diet-induced obesity, we generated mice with a myeloid-specific knockout of carnitine palmitoyltransferase II (CPT2 Mϕ-KO), an obligate step in mitochondrial long-chain fatty acid oxidation. While fatty acid oxidation was clearly induced upon IL-4 stimulation, fatty acid oxidation-deficient CPT2 Mϕ-KO bone marrow-derived macrophages displayed canonical markers of M2 polarization following IL-4 stimulation in vitro...
May 1, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28182011/tak1-regulates-resident-macrophages-by-protecting-lysosomal-integrity
#8
Yosuke Sakamachi, Sho Morioka, September R Mihaly, Giichi Takaesu, Julie F Foley, Michael B Fessler, Jun Ninomiya-Tsuji
Hematopoietic cell survival and death is critical for development of a functional immune system. Here, we report that a protein kinase, TAK1, is selectively required for resident macrophage integrity during embryogenesis. Hematopoietic lineage-specific deletion of Tak1 gene (Tak1(HKO)) caused accumulation of cellular debris in the thymus in perinatal mice. Although no overt alteration in thymocytes and blood myeloid populations was observed in Tak1(HKO) mice, we found that thymic and lung macrophages were diminished...
February 9, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28174696/lack-of-oxyr-and-katg-results-in-extreme-susceptibility-of-francisella-tularensis-lvs-to-oxidative-stress-and-marked-attenuation-in-vivo
#9
Marie Honn, Helena Lindgren, Gurram K Bharath, Anders Sjöstedt
Francisella tularensis is an intracellular bacterium and as such is expected to encounter a continuous attack by reactive oxygen species (ROS) in its intracellular habitat and efficiently coping with oxidative stress is therefore essential for its survival. The oxidative stress response system of F. tularensis is complex and includes multiple antioxidant enzymes and pathways, including the transcriptional regulator OxyR and the H2O2-decomposing enzyme catalase, encoded by katG. The latter is regulated by OxyR...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28159912/identification-of-tbk1-complexes-required-for-the-phosphorylation-of-irf3-and-the-production-of-interferon-%C3%AE
#10
Siddharth Bakshi, Jordan Taylor, Sam Strickson, Thomas McCartney, Philip Cohen
The double-stranded RNA mimetic poly(I:C) and lipopolysaccharide (LPS) activate Toll-like receptors 3 (TLR3) and TLR4, respectively, triggering the activation of TANK (TRAF family member-associated NF-κB activator)-binding kinase 1 (TBK1) complexes, the phosphorylation of interferon regulatory factor 3 (IRF3) and transcription of the interferon β (IFNβ) gene. Here, we demonstrate that the TANK-TBK1 and optineurin (OPTN)-TBK1 complexes control this pathway. The poly(I:C)- or LPS-stimulated phosphorylation of IRF3 at Ser396 and production of IFNβ were greatly reduced in bone marrow-derived macrophages (BMDMs) from TANK knockout (KO) mice crossed to knockin mice expressing the ubiquitin-binding-defective OPTN[D477N] mutant...
March 15, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28151471/nlrp3-inflammasome-activation-mediates-radiation-induced-pyroptosis-in-bone-marrow-derived-macrophages
#11
Yan-Gang Liu, Ji-Kuai Chen, Zi-Teng Zhang, Xiu-Juan Ma, Yong-Chun Chen, Xiu-Ming Du, Hong Liu, Ying Zong, Guo-Cai Lu
A limit to the clinical benefit of radiotherapy is not an incapacity to eliminate tumor cells but rather a limit on its capacity to do so without destroying normal tissue and inducing inflammation. Recent evidence reveals that the inflammasome is essential for mediating radiation-induced cell and tissue damage. In this study, using primary cultured bone marrow-derived macrophages (BMDM) and a mouse radiation model, we explored the role of NLRP3 inflammasome activation and the secondary pyroptosis underlying radiation-induced immune cell death...
February 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28119078/modulation-of-immunological-activity-on-macrophages-induced-by-diazinon
#12
Nanako Ogasawara, Miyoko Matsushima, Nami Kawamura, Kazuko Atsumi, Takehiro Yamaguchi, Haruka Ochi, Yuto Kusatsugu, Sayaka Oyabu, Naozumi Hashimoto, Yoshinori Hasegawa, Jun Ueyama, Tsutomu Kawabe
Diazinon is an organophosphorus (OP) insecticide and is widely used not only in agriculture but also homes and garden in Japan. Diazinon has been reported to increase TNF-α production in rat serum and brain, suggesting that it can modify the proinflammatory response. In this study, we investigated the effects of diazinon on macrophage functions, such as cytokine production, reactive oxygen species (ROS) generation, cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) expressions, cell-surface molecule expressions, and phagocytosis in RAW264...
March 15, 2017: Toxicology
https://www.readbyqxmd.com/read/28106119/early-secreted-antigenic-target-of-6-kda-of-mycobacterium-tuberculosis-stimulates-il-6-production-by-macrophages-through-activation-of-stat3
#13
Bock-Gie Jung, Xisheng Wang, Na Yi, Justin Ma, Joanne Turner, Buka Samten
As early secreted antigenic target of 6 kDa (ESAT-6) of Mycobacterium tuberculosis (Mtb) is an essential virulence factor and macrophages are critical for tuberculosis infection and immunity, we studied ESAT-6 stimulated IL-6 production by macrophages. ESAT-6 stimulated significantly higher IL-6 secretion by murine bone marrow derived macrophages (BMDM) compared to culture filtrate protein 10 kDa (CFP10) and antigen 85A. Polymyxin B, an LPS blocker, did not affect ESAT-6 stimulated macrophage IL-6 production...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28053185/macrophage-ltb4-drives-efficient-phagocytosis-of-borrelia-burgdorferi-via-blt1-or-blt2
#14
Yan Zhang, Rachel M Olson, Charles R Brown
Unresolved experimental Lyme arthritis in C3H 5-lipoxygenase (5-LOX)(-/-) mice is associated with impaired macrophage phagocytosis of Borrelia burgdorferi In the present study, we further investigated the effects of the 5-LOX metabolite, leukotriene (LT)B4 on phagocytosis of B. burgdorferi Bone marrow-derived macrophages (BMDMs) from 5-LOX(-/-) mice were defective in the uptake and killing of B. burgdorferi from the earliest stages of spirochete internalization. BMDMs from mice deficient for the LTB4 high-affinity receptor (BLT1(-/-)) were also unable to efficiently phagocytose B...
March 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28032600/the-function-of-cancer-shed-gangliosides-in-macrophage-phenotype-involvement-with-angiogenesis
#15
Tae-Wook Chung, Hee-Jung Choi, Mi-Ju Park, Hee-Jin Choi, Syng-Ook Lee, Keuk-Jun Kim, Cheorl-Ho Kim, Changwan Hong, Kyun-Ha Kim, Myungsoo Joo, Ki-Tae Ha
Tumor-derived gangliosides in the tumor microenvironment are involved in the malignant progression of cancer. However, the molecular mechanisms underlying the effects of gangliosides shed from tumors on macrophage phenotype remain unknown. Here, we showed that ganglioside GM1 highly induced the activity and expression of arginase-1 (Arg-1), a major M2 macrophage marker, compared to various gangliosides in bone marrow-derived macrophages (BMDM), peritoneal macrophages and Raw264.7 macrophage cells. We found that GM1 bound to macrophage mannose receptor (MMR/CD206) and common gamma chain (γc)...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28001907/ionizing-radiation-induces-innate-immune-responses-in-macrophages-by-generation-of-mitochondrial-reactive-oxygen-species
#16
Sup Kim, Jin Ho Choe, Gippeum Joy Lee, Yi Sak Kim, Soo Yeon Kim, Hye-Mi Lee, Hyo Sun Jin, Tae Sung Kim, Jin-Man Kim, Moon-June Cho, Eui-Cheol Shin, Eun-Kyeong Jo, Jun-Sang Kim
During radiotherapy for tumors, the innate immune system also responds to ionizing radiation and induces immune modulation. However, little is known about the molecular mechanisms by which radiation modulates innate immune responses. In this study, we observed that radiation triggered the generation of mitochondrial reactive oxygen species (mROS), leading to innate immune responses in murine bone marrow-derived macrophages (BMDM). Radiation-induced mROS was essential for robust induction of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-12p40 mRNA and protein in BMDM...
January 2017: Radiation Research
https://www.readbyqxmd.com/read/27987189/immunomodulatory-properties-of-filamentous-fungi-cultivated-through-solid-state-fermentation-on-rapeseed-meal
#17
Stéphanie Sutter, France Thevenieau, Anne Bourdillon, Joëlle De Coninck
Water extracts from solid-state fermentation (SSF) on rapeseed meal using filamentous fungi exhibit interesting immunomodulatory activities in vitro. Immunomodulation was determined by the capacity of the compounds to activate blood neutrophils and to influence cytokine production in human peripheral blood mononuclear cells (PBMC) and mouse bone marrow-derived macrophages (BMDM). Among the strains tested, Aspergillus sojae mycelium and SSF extracts were the most promising in terms of enhancing the immune response...
July 2017: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/27974684/macrophage-production-and-activation-are-dependent-on-trim33
#18
Anne-Sophie Gallouet, Federica Ferri, Vanessa Petit, Aude Parcelier, Daniel Lewandowski, Nathalie Gault, Vilma Barroca, Stéphanie Le Gras, Eric Soler, Frank Grosveld, Irwin Davidson, Paul-Henri Romeo
The tripartite motif (TRIM) family of proteins plays important roles in innate immunity and antimicrobial infection. None of these proteins has been shown to directly regulate transcription of genes in monocyte/macrophage except TRIM33 that we have recently shown to be a macrophage specific transcriptional inhibitor of Ifnb1. Using ChIP-seq analyses, we now report that TRIM33 is bound to two fold more genes in immature than in mature myeloid cell lines. When located near the same genes, TRIM33 is bound to different sequences in the two cell lines suggesting a role of TRIM33 in both immature and mature myeloid cells...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/27933275/an-in-vitro-co-culture-mouse-model-demonstrates-efficient-vaccine-mediated-control-of-francisella-tularensis-schu-s4-and-identifies-nitric-oxide-as-a-predictor-of-efficacy
#19
Igor Golovliov, Helena Lindgren, Kjell Eneslätt, Wayne Conlan, Amandine Mosnier, Thomas Henry, Anders Sjöstedt
Francisella tularensis is a highly virulent intracellular bacterium and cell-mediated immunity is critical for protection, but mechanisms of protection against highly virulent variants, such as the prototypic strain F. tularensis strain SCHU S4, are poorly understood. To this end, we established a co-culture system, based on splenocytes from naïve, or immunized mice and in vitro infected bone marrow-derived macrophages that allowed assessment of mechanisms controlling infection with F. tularensis. We utilized the system to understand why the clpB gene deletion mutant, ΔclpB, of SCHU S4 shows superior efficacy as a vaccine in the mouse model as compared to the existing human vaccine, the live vaccine strain (LVS)...
2016: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/27898698/myeloid-dll4-does-not-contribute-to-the-pathogenesis-of-non-alcoholic-steatohepatitis-in-ldlr-mice
#20
Mike L J Jeurissen, Sofie M A Walenbergh, Tom Houben, Tim Hendrikx, Jieyi Li, Yvonne Oligschlaeger, Patrick J van Gorp, Marion J J Gijbels, Albert Bitorina, Isabell Nessel, Freddy Radtke, Marc Vooijs, Jan Theys, Ronit Shiri-Sverdlov
Non-alcoholic steatohepatitis (NASH) is characterized by liver steatosis and inflammation. Currently, the underlying mechanisms leading to hepatic inflammation are not fully understood and consequently, therapeutic options are poor. Non-alcoholic steatohepatitis (NASH) and atherosclerosis share the same etiology whereby macrophages play a key role in disease progression. Macrophage function can be modulated via activation of receptor-ligand binding of Notch signaling. Relevantly, global inhibition of Notch ligand Delta-Like Ligand-4 (DLL4) attenuates atherosclerosis by altering the macrophage-mediated inflammatory response...
2016: PloS One
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