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Macrophage activation

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https://www.readbyqxmd.com/read/28817691/rac2-is-required-for-alternative-macrophage-activation-and-bleomycin-induced-pulmonary-fibrosis-a-macrophage-autonomous-phenotype
#1
Shweta Joshi, Alok R Singh, Simon S Wong, Muamera Zulcic, Min Jiang, Annie Pardo, Moises Selman, James S Hagood, Donald L Durden
Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by cellular phenotype alterations and deposition of extracellular matrix proteins. The alternative activation of macrophages in the lungs has been associated as a major factor promoting pulmonary fibrosis, however the mechanisms underlying this phenomenon are poorly understood. In the present study, we have defined a molecular mechanism by which signals transmitted from the extracellular matrix via the α4β1 integrin lead to the activation of Rac2 which regulates alternative macrophage differentiation, a signaling axis within the pulmonary macrophage compartment required for bleomycin induced pulmonary fibrosis...
2017: PloS One
https://www.readbyqxmd.com/read/28817687/morphologic-phenotypic-and-transcriptomic-characterization-of-classically-and-alternatively-activated-canine-blood-derived-macrophages-in-vitro
#2
Franziska Heinrich, Annika Lehmbecker, Barbara B Raddatz, Kristel Kegler, Andrea Tipold, Veronika M Stein, Arno Kalkuhl, Ulrich Deschl, Wolfgang Baumgärtner, Reiner Ulrich, Ingo Spitzbarth
Macrophages are a heterogeneous cell population playing a pivotal role in tissue homeostasis and inflammation, and their phenotype strongly depends on the micromilieu. Despite its increasing importance as a translational animal model for human diseases, there is a considerable gap of knowledge with respect to macrophage polarization in dogs. The present study comprehensively investigated the morphologic, phenotypic, and transcriptomic characteristics of unstimulated (M0), M1- (GM-CSF, LPS, IFNγ-stimulated) and M2- (M-CSF, IL-4-stimulated)-polarized canine blood-derived macrophages in vitro...
2017: PloS One
https://www.readbyqxmd.com/read/28817438/alternatively-activated-macrophages-drive-browning-of-white-adipose-tissue-in-burns
#3
Abdikarim Abdullahi, Christopher Auger, Mile Stanojcic, David Patsouris, Alexandra Parousis, Slava Epelman, Marc G Jeschke
OBJECTIVE: The aim of this study was to uncover the mediators and mechanistic events that facilitate the browning of white adipose tissue (WAT) in response to burns. BACKGROUND: In hypermetabolic patients (eg, burns, cancer), the browning of WAT has presented substantial clinical challenges related to cachexia, atherosclerosis, and poor clinical outcomes. Browning of the adipose tissue has recently been found to induce and sustain hypermetabolism. Although browning appears central in trauma-, burn-, or cancer-induced hypermetabolic catabolism, the mediators are essentially unknown...
August 16, 2017: Annals of Surgery
https://www.readbyqxmd.com/read/28817210/varus-knee-osteoarthritis-elevated-synovial-cd15-counts-correlate-with-inferior-biomechanical-properties-of-lateral-compartment-cartilage
#4
Ulrich Koller, Wenzel Waldstein, Veit Krenn, Reinhard Windhager, Friedrich Boettner
The study analyzed the influence of synovitis on the histological and biomechanical properties of lateral-compartment cartilage. In a prospective cohort study, 84 patients (100 knees) with varus deformity of the knee were included. Osteochondral samples from the distal lateral femur underwent biomechanical and histologic analysis. Synovial tissue was sampled for histological (chronic synovitis score) and immunohistochemical evaluation of the degree of synovitis. CD15 (neutrophils), Ki-67 (dividing cells) and CD68 (macrophages) were tested in all synovial samples...
August 17, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28817118/altered-marginal-zone-and-innate-like-b-cells-in-aged-senescence-accelerated-samp8-mice-with-defective-igg1-responses
#5
Isabel Cortegano, Mercedes Rodríguez, Isabel Martín, Maria Carmen Prado, Carolina Ruíz, Rafael Hortigüela, Mario Alía, Marçal Vilar, Helena Mira, Eva Cano, Mercedes Domínguez, Belén de Andrés, María Luisa Gaspar
Aging has a strong impact on the activity of the immune system, enhancing susceptibility to pathogens and provoking a predominant pre-inflammatory status, whereas dampening responses to vaccines in humans and mice. Here, we demonstrate a loss of marginal zone B lymphocytes (MZ, CD19(+)CD45R(+)CD21(++)CD23(lo)) and a decrease of naive B cells (CD19(+)IgD(+)), whereas there is an enhancement of a CD19(+)CD45R(lo) innate-like B cell population (B1REL) and the so-called aged B cell compartment (ABC, CD45R(+)CD21(lo)CD23(lo)CD5(-)CD11b(-)) in aged senescence-accelerated (SAMP8) mice but not in aged senescence-resistant (SAMR1) mice...
August 17, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28817116/total-tanshinones-exhibits-anti-inflammatory-effects-through-blocking-tlr4-dimerization-via-the-myd88-pathway
#6
Hongwei Gao, Xin Liu, Wen Sun, Naixin Kang, Yanli Liu, Shilin Yang, Qiong-Ming Xu, Chunming Wang, Xiuping Chen
Tanshinones belong to a group of lipophilic constituents of Salvia miltiorrhiza Bunge (Danshen), which is widely used in traditional Chinese medicine. A deluge of studies demonstrated that tanshinones exert anti-inflammatory effects, but the underlying mechanisms remain unclear to date. This study investigated the anti-inflammatory effects and mechanisms of total tanshinones (TTN). TTN suppressed the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) and the secretion of TNF-α, IL-6, and IL-1β in RAW264...
August 17, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28816564/cytotoxicity-screening-and-cytokine-profiling-of-nineteen-nanomaterials-enables-hazard-ranking-and-grouping-based-on-inflammogenic-potential
#7
Kunal Bhattacharya, Gözde Kiliç, Pedro M Costa, Bengt Fadeel
Engineered nanomaterials (ENMs) are being produced for an increasing number of applications. Therefore, it is important to assess and categorize ENMs on the basis of their hazard potential. The immune system is the foremost defence against foreign bodies. Here we performed cytokine profiling of a panel of nineteen representative ENMs procured from the Joint Research Centre (JRC) and commercial sources. Physicochemical characterization was performed using dynamic light scattering. The ENMs were all shown to be endotoxin content free...
August 17, 2017: Nanotoxicology
https://www.readbyqxmd.com/read/28816559/the-role-of-the-lectin-like-oxldl-receptor-lox-1-in-traffic-generated-air-pollution-exposure-mediated-alteration-of-the-brain-microvasculature-in-apolipoprotein-apo-e-knockout-mice
#8
JoAnn Lucero, Usa Suwannasual, Lindsay M Herbert, Jacob D McDonald, Amie K Lund
Recent studies have shown a strong correlation between air pollution-exposure and detrimental outcomes in the central nervous system, including alterations in blood brain barrier (BBB) integrity, neuroinflammation, and neurodegeneration. However, the mechanisms mediating these pathologies have not yet been fully elucidated. We have previously reported that exposure to traffic-generated air pollution results in increased circulating oxidized low-density lipoprotein (oxLDL), associated with alterations in BBB integrity, in atherosclerotic Apolipoprotein E null (ApoE(-/-)) mice...
August 17, 2017: Inhalation Toxicology
https://www.readbyqxmd.com/read/28816372/in-vitro-antitubercular-activity-of-3-deoxysappanchalcone-isolated-from-the-heartwood-of-caesalpinia-sappan-linn
#9
Hoonhee Seo, Sukyung Kim, Hafij Al Mahmud, Md Imtiazul Islam, Kung-Woo Nam, Byung-Eui Lee, Hanna Lee, Myoung-Lae Cho, Heung-Mook Shin, Ho-Yeon Song
Responsible for nearly 1.5 million deaths every year, the infectious disease tuberculosis remains one of the most serious challenges to global health. The emergence of multidrug-resistant tuberculosis and, more recently, extensively drug-resistant tuberculosis poses a significant threat in our effort to control this epidemic. New drugs are urgently needed to combat the growing threat of antimicrobial resistance. To achieve this goal, we screened approximately 500 species of medicinal plant methanol extracts and their solvent partitioned fractions for potential inhibitors of Mycobacterium tuberculosis growth...
August 17, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28815947/olive-oil-phenolics-prevent-oxysterol-induced-pro-inflammatory-cytokine-secretion-and-ros-production-in-human-pbmcs-through-modulation-of-p38-and-jnk-pathways
#10
Gessica Serra, Monica Deiana, Jeremy P E Spencer, Giulia Corona
SCOPE: The aim of the present study was to investigate the ability of extra virgin olive oil (EVOO) polyphenols to counteract the pro-inflammatory effects induced by dietary and endogenous oxysterols in ex-vivo immune cells. METHODS AND RESULTS: Peripheral blood mononuclear cells (PBMCs), separated from the whole blood of healthy donors, were utilised and were stimulated with an oxysterols mixture, in the presence of physiologically relevant concentrations of the EVOO polyphenols, hydroxytyrosol (HT), tyrosol (TYR) and homovanillic alcohol (HVA)...
August 16, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28815811/study-of-the-effects-of-spray-drying-in-whey-starch-on-the-probiotic-capacity-of-lactobacillus-rhamnosus-64-in-the-gut-of-mice
#11
L Lavari, P Burns, R Páez, J Reinheimer, G Vinderola
AIMS: To evaluate the effects of spray-drying of Lactobacillus rhamnosus 64 on its capacity to modulate the gut immune response and on the attenuation of TNBS-induced colitis in mice. METHODS AND RESULTS: L. rhamnosus 64 was spray-dried in cheese whey-starch solution and administered to mice for three, six or ten consecutive days. Peritoneal macrophage phagocytic activity, secretory-IgA (S-IgA) levels in the small intestinal fluid and TNFα, IFNγ, IL-10, IL-6 and IL-2 levels in homogenates of the small and large intestine were determined...
August 17, 2017: Journal of Applied Microbiology
https://www.readbyqxmd.com/read/28815559/characteristic-elevation-of-soluble-tnf-receptor-ii-to-i-ratio-in-macrophage-activation-syndrome-with-systemic-juvenile-idiopathic-arthritis
#12
Masaki Shimizu, Natsumi Inoue, Mao Mizuta, Yasuo Nakagishi, Akihiro Yachie
To investigate the clinical significance of soluble tumor necrosis factor receptor (sTNFR) II/I ratio as an indicator of the diagnosis of macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (s-JIA), we measured the serum sTNFRI and II levels in 117 patients with s-JIA, including 29 patients with MAS, 15 with Epstein-Barr virus-induced hemophagocytic lymphohistiocytosis (EBVHLH), 15 with Kawasaki disease (KD), and 28 healthy controls (HCs). We determined their correlation with measurements of disease activity and severity...
August 16, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28815242/-investigation-of-the-effect-of-nuclear-factor-%C3%AE%C2%BAb-on-inflammatory-cell-recruitment-phenotype-of-oral-cancer-associated-macrophage
#13
Xiao-Tian Zhou, Dong Chen, Zhen-Ning Jin, Ke Huang, Jie Lin, Yi Men, Chun-Jie Li
PURPOSE: To explore the ability of nuclear factor κB (NFκB) in sustaining inflammatory cell recruitment phenotype of oral cancer associated macrophages, by using NFκB inhibitor(-Bay11-7082). METHODS: By primary culture, murine macrophages were harvested. Cal27 conditioned medium (CM) and Bay11-7082 were applied for stimulation of the macrophages. RT-PCR and ELISA were used for detecting the inflammatory cell recruitment related chemotactic factors. GraphPadPrism5 was used for statistical analysis...
April 2017: Shanghai Kou Qiang Yi Xue, Shanghai Journal of Stomatology
https://www.readbyqxmd.com/read/28814833/markers-of-oxidative-nitrosative-stress-and-inflammation-in-lung-tissue-of-rats-exposed-to-different-intravenous-iron-compounds
#14
Jorge E Toblli, Gabriel Cao, Jorge F Giani, Fernando P Dominici, Margarita Angerosa
Iron deficiency anemia is a frequent complication in clinical conditions such as chronic kidney disease, chronic heart failure, inflammatory bowel disease, cancer, and excessive blood loss. Given the ability of iron to catalyze redox reactions, iron therapy can be associated with oxidative stress. The lung is uniquely susceptible to oxidative stress, and little is known about the effects of intravenous iron treatment in this organ. This study characterized changes in markers of oxidative/nitrosative stress and inflammation in the lung of non-iron deficient, non-anemic rats treated with five weekly doses (40 mg iron per kg body weight) of low molecular weight iron dextran (LMWID), iron sucrose (IS), ferric carboxymaltose (FCM), ferumoxytol (FMX), iron isomaltoside 1000 (IIM), or saline (control)...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28814641/ceramide-activation-of-rhoa-rho-kinase-impairs-actin-polymerization-during-aggregated-ldl-catabolism
#15
Rajesh K Singh, Abigail S Haka, Alexandria Brumfield, Inna Grosheva, Priya Bhardwaj, Harvey F Chin, Yuquan Xiong, Timothy Hla, Frederick R Maxfield
Macrophages use an extracellular, hydrolytic compartment formed by local actin polymerization to digest aggregated LDL (agLDL). Catabolism of agLDL promotes foam cell formation and creates an environment rich in LDL catabolites including cholesterol and ceramide. Increased ceramide levels are present in lesional LDL, but the effect of ceramide on macrophage pro-atherogenic processes remains unknown. Here, we show that macrophages accumulate ceramide in atherosclerotic lesions. Using macrophages from Sphingosine Kinase 2 knockout (SK2KO) mice to mimic ceramide rich conditions of atherosclerotic lesions, we show that SK2KO macrophages display impaired actin polymerization and foam cell formation in response to contact with agLDL...
August 16, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28814604/macrophage-restricted-shp2-tyrosine-phosphatase-acts-as-a-rheostat-for-mmp12-through-tgf-%C3%AE-activation-in-the-prevention-of-age-related-emphysema-in-mice
#16
Jiaqi Xu, Bo Tao, Xiaohong Guo, Shiyi Zhou, Yongda Li, Yuqin Zhang, Zanhua Zhou, Hongqiang Cheng, Xue Zhang, Yuehai Ke
Persistent activation of macrophages in lungs plays a critical role in the production of matrix metalloproteinases (MMPs) that contributes to the destruction of alveolar walls, a hallmark for pulmonary emphysema. Dysregulated TGF-β1 signaling has been an essential determinant in the elevation of MMPs during the development of emphysema. Nevertheless, the mechanism for this MMP-dependent pathogenesis has yet to be clearly investigated. Recently, we identified an important role for tyrosine phosphatase Src homology domain-containing protein tyrosine phosphatase 2 (Shp2) in regulating the activation of alveolar macrophages...
August 16, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28814429/nintedanib-macrophage-activation-and-ameliorates-vascular-and-fibrotic-manifestations-in-the-fra2-mouse-model-of-systemic-sclerosis
#17
Jingang Huang, Christiane Maier, Yun Zhang, Alina Soare, Clara Dees, Christian Beyer, Ulrike Harre, Chih-Wei Chen, Oliver Distler, Georg Schett, Lutz Wollin, Jörg H W Distler
BACKGROUND: Nintedanib is an inhibitor targeting platelet-derived growth factor receptor, fibroblast growth factor receptor and vascular endothelial growth factor receptor tyrosine kinases that has recently been approved for the treatment of idiopathic pulmonary fibrosis. The aim of this study was to analyse the effects of nintedanib in the fos-related antigen-2 (Fra2) mouse model of systemic sclerosis (SSc). METHODS: The effects of nintedanib on pulmonary arterial hypertension with proliferation of pulmonary vascular smooth muscle cells (PVSMCs) and luminal occlusion, on microvascular disease with apoptosis of microvascular endothelial cells (MVECs) and on fibroblast activation with myofibroblast differentiation and accumulation of extracellular matrix were analysed...
August 16, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28813715/induction-of-cyclooxygenase-2-by-streptococcus-pyogenes-is-mediated-by-cytolysins
#18
Ulrike Blaschke, Andreas Beineke, Johanna Klemens, Eva Medina, Oliver Goldmann
Prostaglandin E2 (PGE2), an arachidonic acid metabolite regulating a broad range of physiological activities, is an important modulator of the severity of infection caused by Streptococcus pyogenes. Here, we investigated the role of streptococcal cytolysin S (SLS) and streptococcal cytolysin O (SLO) in the induction of cyclooxygenase-2 (COX-2), the rate-limiting enzyme in the synthesis of prostaglandins, in in vitro cultured macrophages and during in vivo infection. Macrophages were infected with S. pyogenes wild type or with the isogenic mutant strains deficient in SLS (ΔSLS), SLO (ΔSLO), or both (ΔSLS/ΔSLO), and the expression of COX-2 was determined at the transcriptional and the protein level...
August 17, 2017: Journal of Innate Immunity
https://www.readbyqxmd.com/read/28813676/pharmacologic-or-genetic-targeting-of-glutamine-synthetase-skews-macrophages-toward-an-m1-like-phenotype-and-inhibits-tumor-metastasis
#19
Erika M Palmieri, Alessio Menga, Rosa Martín-Pérez, Annamaria Quinto, Carla Riera-Domingo, Giacoma De Tullio, Douglas C Hooper, Wouter H Lamers, Bart Ghesquière, Daniel W McVicar, Attilio Guarini, Massimiliano Mazzone, Alessandra Castegna
Glutamine-synthetase (GS), the glutamine-synthesizing enzyme from glutamate, controls important events, including the release of inflammatory mediators, mammalian target of rapamycin (mTOR) activation, and autophagy. However, its role in macrophages remains elusive. We report that pharmacologic inhibition of GS skews M2-polarized macrophages toward the M1-like phenotype, characterized by reduced intracellular glutamine and increased succinate with enhanced glucose flux through glycolysis, which could be partly related to HIF1α activation...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28813657/interferon-%C3%AE-represses-m2-gene-expression-in-human-macrophages-by-disassembling-enhancers-bound-by-the-transcription-factor-maf
#20
Kyuho Kang, Sung Ho Park, Janice Chen, Yu Qiao, Eugenia Giannopoulou, Karen Berg, Adedayo Hanidu, Jun Li, Gerald Nabozny, Keunsoo Kang, Kyung-Hyun Park-Min, Lionel B Ivashkiv
Mechanisms by which interferon (IFN)-γ activates genes to promote macrophage activation are well studied, but little is known about mechanisms and functions of IFN-γ-mediated gene repression. We used an integrated transcriptomic and epigenomic approach to analyze chromatin accessibility, histone modifications, transcription-factor binding, and gene expression in IFN-γ-primed human macrophages. IFN-γ suppressed basal expression of genes corresponding to an "M2"-like homeostatic and reparative phenotype. IFN-γ repressed genes by suppressing the function of enhancers enriched for binding by transcription factor MAF...
August 15, 2017: Immunity
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