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https://www.readbyqxmd.com/read/29317502/macrophages-with-a-deletion-of-the-phosphoenolpyruvate-carboxykinase-1-pck1-gene-have-a-more-proinflammatory-phenotype
#1
Chih-Wei Ko, Daniel Counihan, Jing Wu, Maria Hatzoglou, Michelle A Puchowicz, Colleen M Croniger
Phosphoenolpyruvate carboxykinase (Pck1) is a metabolic enzyme that is integral to the gluconeogenic and glyceroneogenic pathway. However, the role of Pck1 in macrophage metabolism and function is unknown. Using stable isotopomer MS analysis in a mouse model with a myeloid cell specific Pck1 deletion, we show here that this deletion increases the proinflammatory phenotype in macrophages. Incubation of LPS-stimulated bone marrow derived macrophages (BMDM) with [U-13C] glucose revealed reduced [13C] labeling of citrate and malate and increased [13C] labeling of lactate in Pck1 deleted BMDMs...
January 9, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29279328/hydrogen-sulfide-inhibits-the-nlrp3-inflammasome-and-reduces-cytokine-production-both-in-vitro-and-in-a-mouse-model-of-inflammation
#2
Mariela Castelblanco, Jérôme Lugrin, Driss Ehirchiou, Sonia Nasi, Isao Ishii, Alexander So, Fabio Martinon, Nathalie Busso
A variety of stimuli, including monosodium urate (MSU) crystals, activate the NLRP3 inflammasome, and this activation involves several molecular mechanisms including xanthine oxidase (XO) upregulation and mitochondrial dysfunction. Upon oligomerization of apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1 becomes active and cleaves the proinflammatory cytokine IL-1β into its active secreted form. Hydrogen sulfide (H2S), a gasotransmitter mainly produced by cystathionine γ-lyase (CSE) in macrophages, could modulate inflammation...
December 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29230347/induction-of-reactive-intermediates-and-autophagy-related-proteins-upon-infection-of-macrophages-with-rhodococcus-equi
#3
Prashanth Chandramani-Shivalingappa, Mahesh Bhandari, Sarah A Wiechert, Jessica Gilbertie, Douglas E Jones, Brett A Sponseller
Rhodococcus equi (R. equi) is an intracellular macrophage-tropic pathogen with potential for causing fatal pyogranulomatous pneumonia in foals between 1 and 6 months of age. In this study, we sought to determine whether infection of macrophages with R. equi could lead to the induction of autophagy. Murine bone marrow derived macrophages (BMDM) were infected with R. equi for various time intervals and analyzed for upregulation of autophagy proteins and accumulation of autophagosomes relative to uninfected controls...
2017: Scientifica
https://www.readbyqxmd.com/read/29217193/regulation-of-inflammatory-gene-expression-in-macrophages-by-epithelial-stromal-interaction-1-epsti1
#4
Young-Hoon Kim, Jae-Rin Lee, Myong-Joon Hahn
Epithelial-stromal interaction 1 (EPSTI1) was first discovered as a gene induced in breast cancer epithelial cells by co-cultured stromal fibroblasts. There are many reports on the role of Epsti1 in cancer malignancy. Epsti1 is now well known in regulating cancer. Recently, the role of Epsti1 in the immune response has been reported; these reports suggest the role of Epsti1 in immune function, immune privilege, and autoimmune diseases. Furthermore, they show that Epsti1 is expressed in various types of immune cells...
December 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29175486/targeting-the-15-keto-pge2-ptgr2-axis-modulates-systemic-inflammation-and-survival-in-experimental-sepsis
#5
Ing-Jung Chen, Siow-Wey Hee, Chun-Hsing Liao, Shih-Yao Lin, Lynn Su, Chia-Tung Shun, Lee-Ming Chuang
Sepsis is a systemic inflammation accompanied by multi-organ dysfunction due to microbial infection. Prostaglandins and their metabolites have long been studied for their importance in regulating the innate immune response. 15-keto-PGE2 (15k-PGE2) is a prostaglandin E2 (PGE2) metabolite, whose further processing is catalyzed by prostaglandin reductase 2 (PTGR2). We showed disruption of the Ptgr2 gene in mice improves the survival rate under both LPS- and cecum ligation/puncture (CLP)-induced experimental sepsis...
November 22, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29138422/fam19a5-a-brain-specific-chemokine-inhibits-rankl-induced-osteoclast-formation-through-formyl-peptide-receptor-2
#6
Min Young Park, Hyung Sik Kim, Mingyu Lee, Byunghyun Park, Ha Young Lee, Eun Bee Cho, Jae Young Seong, Yoe-Sik Bae
Osteoclasts can be differentiated from bone marrow-derived macrophages (BMDM). They play a key role in bone resorption. Identifying novel molecules that can regulate osteoclastogenesis has been an important issue. In this study, we found that FAM19A5, a neurokine or brain-specific chemokine, strongly stimulated mouse BMDM, resulting in chemotactic migration and inhibition of RANKL-induced osteoclastogenesis. Expression levels of osteoclast-related genes such as RANK, TRAF6, OSCAR, TRAP, Blimp1, c-fos, and NFATc1 were markedly decreased by FAM19A5...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29097606/deletion-of-neuropilin-1-from-microglia-or-bone-marrow-derived-macrophages-slows-glioma-progression
#7
Jeremy T Miyauchi, Michael D Caponegro, Danling Chen, Matthew K Choi, Melvin Li, Stella E Tsirka
Glioma-associated microglia and macrophages (GAM) which infiltrate high-grade gilomas represent constitute a major cellular component of these lesions. GAM behavior is influenced by tumor-derived cytokines that suppress initial anti-tumorigenic properties, causing them to support tumor growth and to convert and suppress adaptive immune responses to the tumor. Mice which lack the transmembrane receptor neuropilin-1 (Nrp1) which modulates GAM immune polarization exhibit a decrease in glioma volumes and neoangiogenesis and an increase in anti-tumorigenic GAM infiltrate...
November 2, 2017: Cancer Research
https://www.readbyqxmd.com/read/29077752/isg15-governs-mitochondrial-function-in-macrophages-following-vaccinia-virus-infection
#8
Sara Baldanta, Mercedes Fernández-Escobar, Rebeca Acín-Perez, Manuel Albert, Emilio Camafeita, Inmaculada Jorge, Jesús Vázquez, José Antonio Enríquez, Susana Guerra
The interferon (IFN)-stimulated gene 15 (ISG15) encodes one of the most abundant proteins induced by interferon, and its expression is associated with antiviral immunity. To identify protein components implicated in IFN and ISG15 signaling, we compared the proteomes of ISG15-/- and ISG15+/+ bone marrow derived macrophages (BMDM) after vaccinia virus (VACV) infection. The results of this analysis revealed that mitochondrial dysfunction and oxidative phosphorylation (OXPHOS) were pathways altered in ISG15-/- BMDM treated with IFN...
October 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29042581/immunoproteasome-subunit-%C3%A3-5i-lmp7-deficiency-in-atherosclerosis
#9
Bernd Hewing, Antje Ludwig, Cristian Dan, Max Pötzsch, Carmen Hannemann, Andreas Petry, Dilyara Lauer, Agnes Görlach, Elena Kaschina, Dominik N Müller, Gert Baumann, Verena Stangl, Karl Stangl, Nicola Wilck
Management of protein homeostasis by the ubiquitin-proteasome system is critical for atherosclerosis development. Recent studies showed controversial results on the role of immunoproteasome (IP) subunit β5i/LMP7 in maintenance of protein homeostasis under cytokine induced oxidative stress. The present study aimed to investigate the effect of β5i/LMP7-deficiency on the initiation and progression of atherosclerosis as a chronic inflammatory, immune cell driven disease. LDLR(-/-)LMP7(-/-) and LDLR(-/-) mice were fed a Western-type diet for either 6 or 24 weeks to induce early and advanced stage atherosclerosis, respectively...
October 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29038439/analysis-of-nkx3-1-cre-driven-erk5-deletion-reveals-a-profound-spinal-deformity-which-is-linked-to-increased-osteoclast-activity
#10
Carolyn J Loveridge, Rob J van 't Hof, Gemma Charlesworth, Ayala King, Ee Hong Tan, Lorraine Rose, Anna Daroszewska, Amanda Prior, Imran Ahmad, Michelle Welsh, Ernest J Mui, Catriona Ford, Mark Salji, Owen Sansom, Karen Blyth, Hing Y Leung
Extracellular signal-regulated protein kinase 5 (ERK5) has been implicated during development and carcinogenesis. Nkx3.1-mediated Cre expression is a useful strategy to genetically manipulate the mouse prostate. While grossly normal at birth, we observed an unexpected phenotype of spinal protrusion in Nkx3.1:Cre;Erk5 (fl/fl) (Erk5 (fl/fl)) mice by ~6-8 weeks of age. X-ray, histological and micro CT (µCT) analyses showed that 100% of male and female Erk5 (fl/fl) mice had a severely deformed curved thoracic spine, with an associated loss of trabecular bone volume...
October 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28974200/selection-of-reliable-reference-genes-for-the-normalisation-of-gene-expression-levels-following-time-course-lps-stimulation-of-murine-bone-marrow-derived-macrophages
#11
Akane Tanaka, Joyce To, Bronwyn O'Brien, Sheila Donnelly, Maria Lund
BACKGROUND: Macrophages are key players in the initiation, perpetuation and regulation of both innate and adaptive immune responses. They largely perform these roles through modulation of the expression of genes, especially those encoding cytokines. Murine bone marrow derived macrophages (BMDMs) are commonly used as a model macrophage population for the study of immune responses to pro-inflammatory stimuli, notably lipopolysaccharide (LPS), which may be pertinent to the human situation...
October 3, 2017: BMC Immunology
https://www.readbyqxmd.com/read/28974092/poly-i-c-encapsulating-nanoparticles-enhance-innate-immune-responses-to-the-tuberculosis-vaccine-bacille-calmette-gu%C3%A3-rin-bcg-via-synergistic-activation-of-innate-immune-receptors
#12
Martin T Speth, Urska Repnik, Elisabeth Müller, Julia Spanier, Ulrich Kalinke, Alexandre Corthay, Gareth Griffiths
The attenuated live vaccine strain bacille Calmette-Guérin (BCG) is currently the only available vaccine against tuberculosis (TB), but is largely ineffective against adult pulmonary TB, the most common disease form. This is in part due to BCG's ability to interfere with the host innate immune response, a feature that might be targeted to enhance the potency of this vaccine. Here, we investigated the ability of chitosan-based nanoparticles (pIC-NPs) containing polyinosinic-polycytidylic acid (poly(I:C)), an inducer of innate immunity via Toll-like receptor 3 (TLR3), to enhance the immunogenicity of BCG in mouse bone marrow derived macrophages (BMDM) in vitro...
November 6, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28940384/lipid-homeostasis-and-inflammatory-activation-are-disturbed-in-classically-activated-macrophages-with-peroxisomal-%C3%AE-oxidation-deficiency
#13
Ivana Geric, Yulia Y Tyurina, Olga Krysko, Dmitri V Krysko, Evelyn De Schryver, Valerian E Kagan, Paul P Van Veldhoven, Myriam Baes, Simon Verheijden
Macrophage activation is characterized by pronounced metabolic adaptation. Classically activated macrophages show decreased rates of mitochondrial fatty acid oxidation and oxidative phosphorylation and acquire a glycolytic state together with their pro-inflammatory phenotype. In contrast, alternatively activated macrophages require oxidative phosphorylation and mitochondrial fatty acid oxidation for their anti-inflammatory function. Although it is evident that mitochondrial metabolism is regulated during macrophage polarization and essential for macrophage function, little is known on the regulation and role of peroxisomal β-oxidation during macrophage activation...
September 22, 2017: Immunology
https://www.readbyqxmd.com/read/28912382/versican-is-produced-by-trif-and-type-i-interferon-dependent-signaling-in-macrophages-and-contributes-to-fine-control-of-innate-immunity-in-lungs
#14
Mary Y Chang, Inkyung Kang, Michael Gale, Anne M Manicone, Michael G Kinsella, Kathleen R Braun, Tara Wigmosta, William C Parks, William A Altemeier, Thomas N Wight, Charles W Frevert
Growing evidence suggests that versican is important in the innate immune response to lung infection. Our goal was to understand the regulation of macrophage-derived versican and the role it plays in innate immunity. We first defined the signaling events that regulate versican expression using bone marrow derived macrophages (BMDM) from mice lacking specific Toll-like receptors (TLR), TLR adaptor molecules or the type I interferon receptor (IFNAR1). We show that LPS and polyinosinic-polycytidylic acid [Poly(I:C)] trigger a signaling cascade involving TLR3 or 4, the Trif adaptor, Type I interferons and IFNAR1, leading to increased expression of versican by macrophages and implicating versican as an interferon-stimulated gene...
September 14, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28903728/increased-survival-and-proliferation-of-the-epidemic-strain-mycobacterium-abscessus-subsp-massiliense-crm0019-in-alveolar-epithelial-cells
#15
Giovanni Monteiro Ribeiro, Cristianne Kayoko Matsumoto, Fernando Real, Daniela Teixeira, Rafael Silva Duarte, Renato Arruda Mortara, Sylvia Cardoso Leão, Cristiane de Souza Carvalho-Wodarz
BACKGROUND: Outbreaks of infections caused by rapidly growing mycobacteria have been reported worldwide generally associated with medical procedures. Mycobacterium abscessus subsp. massiliense CRM0019 was obtained during an epidemic of postsurgical infections and was characterized by increased persistence in vivo. To better understand the successful survival strategies of this microorganism, we evaluated its infectivity and proliferation in macrophages (RAW and BMDM) and alveolar epithelial cells (A549)...
September 13, 2017: BMC Microbiology
https://www.readbyqxmd.com/read/28887514/dormant-5-lipoxygenase-in-inflammatory-macrophages-is-triggered-by-exogenous-arachidonic-acid
#16
Carlos A Sorgi, Simona Zarini, Sarah A Martin, Raphael L Sanchez, Rodrigo F Scandiuzzi, Miguel A Gijón, Carlos Guijas, Nicolas Flamand, Robert C Murphy, Lucia H Faccioli
The differentiation of resident tissue macrophages from embryonic precursors and that of inflammatory macrophages from bone marrow cells leads to macrophage heterogeneity. Further plasticity is displayed through their ability to be polarized as subtypes M1 and M2 in a cell culture microenvironment. However, the detailed regulation of eicosanoid production and its involvement in macrophage biology remains unclear. Using a lipidomics approach, we demonstrated that eicosanoid production profiles between bone marrow-derived (BMDM) and peritoneal macrophages differed drastically...
September 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28886148/balancing-anti-inflammatory-and-anti-oxidant-responses-in-murine-bone-marrow-derived-macrophages
#17
Christopher R Nitkin, Tracey L Bonfield
RATIONALE: The underlying pathophysiology of bronchopulmonary dysplasia includes a macrophage-mediated host response orchestrated by anti-inflammatory peroxisome proliferator-activated receptor gamma (PPARγ) and anti-oxidant nuclear factor (erythroid-derived 2)-like 2 (Nrf2). These have not yet been studied in combination. This study tested the hypothesis that combined inflammatory and oxidative stressors would interact and change PPARγ- and Nrf2-regulated gene expression and antioxidant capacity...
2017: PloS One
https://www.readbyqxmd.com/read/28855315/eplerenone-prevented-obesity-induced-inflammasome-activation-and-glucose-intolerance
#18
Tsutomu Wada, Akari Ishikawa, Eri Watanabe, Yuto Nakamura, Yusuke Aruga, Hayate Hasegawa, Yasuhiro Onogi, Hiroe Honda, Yoshinori Nagai, Kiyoshi Takatsu, Yoko Ishii, Masakiyo Sasahara, Daisuke Koya, Hiroshi Tsuneki, Toshiyasu Sasaoka
Obesity-associated activation of the renin-angiotensin-aldosterone system is implicated in the pathogenesis of insulin resistance; however, influences of mineralocorticoid receptor (MR) inhibition remain unclear. Therefore, we aimed to clarify the anti-inflammatory mechanisms of MR inhibition using eplerenone, a selective MR antagonist, in C57BL/6 mice fed a high-fat diet (HFD) for 12 weeks. Eplerenone prevented excessive body weight gain and fat accumulation, ameliorated glucose intolerance and insulin resistance and enhanced energy metabolism...
December 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28810254/insulin-influences-lps-induced-tnf-%C3%AE-and-il-6-release-through-distinct-pathways-in-mouse-macrophages-from-different-compartments
#19
Fernando H G Tessaro, Thais S Ayala, Eduardo L Nolasco, Leonardo M Bella, Joilson O Martins
BACKGROUND/AIMS: Diabetic subjects are more susceptible to infections, which is partially due to insulin deficiency and hyperglycemia. We hypothesized that insulin influences cytokine release by macrophages from diabetic C57BL/6 mice stimulated with lipopolysaccharides (LPS). METHODS: Bone marrow-derived macrophages (BMDM) and tissue-specific macrophages from diabetic (alloxan 60 mg/kg, i.v.) male C57BL/6 mice were stimulated by LPS (100 ng/mL) and/or treated by insulin (1 mU/mL)...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28776122/mechanisms-involved-in-the-remyelinating-effect-of-sildenafil
#20
Daniela Díaz-Lucena, María Gutierrez-Mecinas, Beatriz Moreno, José Lupicinio Martínez-Sánchez, Paula Pifarré, Agustina García
Remyelination occurs in demyelinated lesions in multiple sclerosis (MS) and pharmacological treatments that enhance this process will critically impact the long term functional outcome in the disease. Sildenafil, a cyclic GMP (cGMP)-specific phosphodiesterase 5 inhibitor (PDE5-I), is an oral vasodilator drug extensively used in humans for treatment of erectile dysfunction and pulmonary arterial hypertension. PDE5 is expressed in central nervous system (CNS) neuronal and glial populations and in endothelial cells and numerous studies in rodent models of neurological disease have evidenced the neuroprotective potential of PDE5-Is...
August 3, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
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