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https://www.readbyqxmd.com/read/28098757/role-of-mir-34a-5p-in-hematopoietic-progenitor-cells-proliferation-and-fate-decision-novel-insights-into-the-pathogenesis-of-primary-myelofibrosis
#1
Elisa Bianchi, Samantha Ruberti, Sebastiano Rontauroli, Paola Guglielmelli, Simona Salati, Chiara Rossi, Roberta Zini, Enrico Tagliafico, Alessandro Maria Vannucchi, Rossella Manfredini
Primary Myelofibrosis (PMF) is a chronic Philadelphia-negative myeloproliferative neoplasm characterized by a skewed megakaryopoiesis and an overproduction of proinflammatory and profibrotic mediators that lead to the development of bone marrow (BM) fibrosis. Since we recently uncovered the upregulation of miR-34a-5p in PMF CD34+ hematopoietic progenitor cells (HPCs), in order to elucidate its role in PMF pathogenesis here we unravelled the effects of miR-34a-5p overexpression in HPCs. We showed that enforced expression of miR-34a-5p partially constrains proliferation and favours the megakaryocyte and monocyte/macrophage commitment of HPCs...
January 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28095306/the-role-of-pten-in-regulation-of-hepatic-macrophages-activation-and-function-in-progression-and-reversal-of-liver-fibrosis
#2
Yahui Cheng, Yuanyao Tian, Jialu Xia, Xiaoqin Wu, Yang Yang, Xiaofeng Li, Cheng Huang, Xiaoming Meng, Taotao Ma, Jun Li
Activation of Kupffer cells (KCs) plays a pivotal role in the pathogenesis of liver fibrosis. The progression and reversal of CCl4-induced mouse liver fibrosis showed a mixed induction of hepatic classical (M1) and alternative (M2) macrophage markers. Although the role of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in modulating myeloid cell activation has recently been identified, its function in macrophage activation during hepatic fibrosis remains to be fully appreciated. In our study, PTEN expression of KCs was remarkably decreased in CCl4-induced mice but increased to a near-normal level in reversed mice...
January 14, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28093527/human-cystic-fibrosis-macrophages-have-defective-calcium-dependent-protein-kinase-c-activation-of-the-nadph-oxidase-an-effect-augmented-by-burkholderia-cenocepacia
#3
Kaivon Assani, Chandra L Shrestha, Frank Robledo-Avila, Murugesan V Rajaram, Santiago Partida-Sanchez, Larry S Schlesinger, Benjamin T Kopp
Macrophage intracellular pathogen killing is defective in cystic fibrosis (CF), despite abundant production of reactive oxygen species (ROS) in lung tissue. Burkholderia species can cause serious infection in CF and themselves affect key oxidase components in murine non-CF cells. However, it is unknown whether human CF macrophages have an independent defect in the oxidative burst and whether Burkholderia contributes to this defect in terms of assembly of the NADPH oxidase complex and subsequent ROS production...
January 16, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28091914/altered-liver-proteoglycan-glycosaminoglycan-structure-as-a-manifestation-of-extracellular-matrix-remodeling-upon-bcg-induced-granulomatosis-in-mice
#4
L B Kim, V A Shkurupy, A N Putyatina
Experimental BCG-induced granulomatosis in mice was used to study changes in the dynamics of individual liver proteoglycan components reflecting phasic extracellular matrix remodeling, determined by the host-parasite interaction and associated with granuloma development. In the early BCG-granulomatosis period, the increase in individual proteoglycan components promotes granuloma formation, providing conditions for mycobacteria adhesion to host cells, migration of phagocytic cells from circulation, and cell-cell interaction leading to granuloma development and fibrosis...
January 14, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28090562/hepatitis-c-virus-induced-monocyte-differentiation-into-polarized-m2-macrophages-promotes-stellate-cell-activation-via%C3%A2-tgf-%C3%AE
#5
Banishree Saha, Karen Kodys, Gyongyi Szabo
BACKGROUND & AIMS: Monocyte and macrophage (MΦ) activation contributes to the pathogenesis of chronic hepatitis C virus (HCV) infection. Disease pathogenesis is regulated by both liver-resident MΦs and monocytes recruited as precursors of MΦs into the damaged liver. Monocytes differentiate into M1 (classic/proinflammatory) or M2 (alternative/anti-inflammatory) polarized MΦs in response to tissue microenvironment. We hypothesized that HCV-infected hepatoma cells (infected with Japanese fulminant hepatitis-1 [Huh7...
May 2016: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28086885/harnessing-the-early-post-injury-inflammatory-responses-for-cardiac-regeneration
#6
REVIEW
Bill Cheng, H C Chen, I W Chou, Tony W H Tang, Patrick C H Hsieh
Cardiac inflammation is considered by many as the main driving force in prolonging the pathological condition in the heart after myocardial infarction. Immediately after cardiac ischemic injury, neutrophils are the first innate immune cells recruited to the ischemic myocardium within the first 24 h. Once they have infiltrated the injured myocardium, neutrophils would then secret proteases that promote cardiac remodeling and chemokines that enhance the recruitment of monocytes from the spleen, in which the recruitment peaks at 72 h after myocardial infarction...
January 13, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28079883/cysteamine-re-establishes-the-clearance-of-pseudomonas-aeruginosa-by-macrophages-bearing-the-cystic-fibrosis-relevant-f508del-cftr-mutation
#7
Eleonora Ferrari, Romina Monzani, Valeria R Villella, Speranza Esposito, Francesca Saluzzo, Federica Rossin, Manuela D'Eletto, Antonella Tosco, Fabiola De Gregorio, Valentina Izzo, Maria C Maiuri, Guido Kroemer, Valeria Raia, Luigi Maiuri
Cystic fibrosis (CF), the most common lethal monogenic disease in Caucasians, is characterized by recurrent bacterial infections and colonization, mainly by Pseudomonas aeruginosa, resulting in unresolved airway inflammation. CF is caused by mutations in the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein, which functions as a chloride channel in epithelial cells, macrophages, and other cell types. Impaired bacterial handling by macrophages is a feature of CF airways, although it is still debated how defective CFTR impairs bacterial killing...
January 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28077599/blt1-mediates-bleomycin-induced-lung-fibrosis-independently-of-neutrophils-and-cd4-t-cells
#8
Jiaoyan Lv, Yingluo Xiong, Wenjing Li, Wei Yang, Lina Zhao, Rui He
Leukotriene B4 (LTB4) and its functional receptor BLT1 are closely involved in tissue inflammation by primarily mediating leukocyte recruitment and activation. Elevated LTB4 was reported in patients with lung fibrosis; however, the role of the LTB4/BLT1 axis in lung fibrosis remains unknown. In this study, we demonstrated that BLT1(-/-) mice exhibited significantly attenuated bleomycin (BLM)-induced lung fibrosis. Interestingly, BLT1 blockade with its specific antagonist U75302 in the acute injury phase (days 0-10 after BLM treatment) significantly attenuated lung fibrosis, which was accompanied by significant decreases in early infiltrating neutrophils and later infiltrating CD4(+) T cells and the production of TGF-β, IL-13, and IL-17A...
January 11, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28075404/advanced-oxidation-protein-products-modified-albumin-induces-differentiation-of-raw264-7-macrophages-into-dendritic-like-cells-which-is-modulated-by-cell-surface-thiols
#9
Silvano Garibaldi, Chiara Barisione, Barbara Marengo, Pietro Ameri, Claudio Brunelli, Manrico Balbi, Giorgio Ghigliotti
Local accumulation of Advanced Oxidation Protein Products (AOPP) induces pro-inflammatory and pro-fibrotic processes in kidneys and is an independent predictor of renal fibrosis and of rapid decline of eGFR in patients with chronic kidney disease (CKD). In addition to kidney damage, circulating AOPP may be regarded as mediators of systemic oxidative stress and, in this capacity, they might play a role in the progression of atherosclerotic damage of arterial walls. Atherosclerosis is a chronic inflammatory disease that involves activation of innate and adaptive immunity...
January 10, 2017: Toxins
https://www.readbyqxmd.com/read/28075361/role-of-ire1%C3%AE-xbp-1-in-cystic-fibrosis-airway-inflammation
#10
REVIEW
Carla M P Ribeiro, Bob A Lubamba
Cystic fibrosis (CF) pulmonary disease is characterized by chronic airway infection and inflammation. The infectious and inflamed CF airway environment impacts on the innate defense of airway epithelia and airway macrophages. The CF airway milieu induces an adaptation in these cells characterized by increased basal inflammation and a robust inflammatory response to inflammatory mediators. Recent studies have indicated that these responses depend on activation of the unfolded protein response (UPR). This review discusses the contribution of airway epithelia and airway macrophages to CF airway inflammatory responses and specifically highlights the functional importance of the UPR pathway mediated by IRE1/XBP-1 in these processes...
January 9, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28069067/end-stage-cystic-fibrosis-lung-disease-is-characterised-by-a-diverse-inflammatory-pattern-an-immunohistochemical-analysis
#11
Elise J Lammertyn, Elly Vandermeulen, Hannelore Bellon, Stephanie Everaerts, Stijn E Verleden, Kathleen Van Den Eynde, Ken R Bracke, Guy G Brusselle, Pieter C Goeminne, Erik K Verbeken, Bart M Vanaudenaerde, Lieven J Dupont
BACKGROUND: Cystic fibrosis (CF) lung disease is characterised by vigorous airway inflammation eventually resulting in severe lung damage. This study aimed to describe the diversity of the inflammatory pattern in end-stage CF lungs by evaluating and quantifying which components of the innate and adaptive immunity are involved, and by assessing whether this is gender-specific. METHODS: CF explant lung tissue (n = 20) collected at time of transplantation and control tissue (n = 22) was sectioned (9 μm) and stained for neutrophils, eosinophils, mast cells, dendritic cells, macrophages, CD4 T cells, cytotoxic T cells and B cells...
January 10, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28060908/experimental-mouse-model-of-lumbar-ligamentum-flavum-hypertrophy
#12
Takeyuki Saito, Kazuya Yokota, Kazu Kobayakawa, Masamitsu Hara, Kensuke Kubota, Katsumi Harimaya, Kenichi Kawaguchi, Mitsumasa Hayashida, Yoshihiro Matsumoto, Toshio Doi, Keiichiro Shiba, Yasuharu Nakashima, Seiji Okada
Lumbar spinal canal stenosis (LSCS) is one of the most common spinal disorders in elderly people, with the number of LSCS patients increasing due to the aging of the population. The ligamentum flavum (LF) is a spinal ligament located in the interior of the vertebral canal, and hypertrophy of the LF, which causes the direct compression of the nerve roots and/or cauda equine, is a major cause of LSCS. Although there have been previous studies on LF hypertrophy, its pathomechanism remains unclear. The purpose of this study is to establish a relevant mouse model of LF hypertrophy and to examine disease-related factors...
2017: PloS One
https://www.readbyqxmd.com/read/28052876/pericyte-and-immune-cells-contribute-to-complement-activation-in-tubulointerstitial-fibrosis
#13
Sandhya Xavier, Ranjit K Sahu, Susan G Landes, Jing Yu, Ronald P Taylor, Srinivas Ayyadevara, Judit Megyesi, William B Stallcup, Jeremy S Duffield, Edimara S Reis, John D Lambris, Didier Portilla
We have examined the pathogenic role of increased complement expression and activation during kidney fibrosis. Here we show that PDGFRβ positive pericytes isolated from mice subjected to obstructive or folic acid injury secrete C1q. This was associated with increased production of proinflammatory cytokines, extracellular matrix components, collagens and increased Wnt3a-mediated activation of Wnt/β-catenin signaling, that are hallmarks of myofibroblast activation. Real-time PCR, immunoblots, immunohistochemistry and flow cytometry analysis performed in whole kidney tissue confirmed increased expression of C1q, C1r, C1s as well as complement activation measured as increased synthesis of C3 fragments predominantly in the interstitial compartment...
January 4, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28051792/-u-u-%C3%A2-management-strategies-for-liver-fibrosis
#14
Alejandra Altamirano-Barrera, Beatriz Barranco-Fragoso, Nahum Méndez-Sánchez
 Liver fibrosis resulting from chronic liver injury are major causes of morbidity and mortality worldwide. Among causes of hepatic fibrosis, viral infection is most common (hepatitis B and C). In addition, obesity rates worldwide have accelerated the risk of liver injury due to nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Also liver fibrosis is associated with the consumption of alcohol, or autoimmune hepatitis and chronic cholangiophaties. The response of hepatocytes to inflammation plays a decisive role in the physiopathology of hepatic fibrosis, which involves the recruitment of both pro- and anti-inflammatory cells such as monocytes and macrophages...
January 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/28046077/an-oxygen-sensing-two-component-system-in-the-burkholderia-cepacia-complex-regulates-biofilm-intracellular-invasion-and-pathogenicity
#15
Matthew M Schaefers, Tiffany L Liao, Nicole M Boisvert, Damien Roux, Deborah Yoder-Himes, Gregory P Priebe
Burkholderia dolosa is a member of the Burkholderia cepacia complex (BCC), which is a group of bacteria that cause chronic lung infection in patients with cystic fibrosis (CF) and can be associated with outbreaks carrying high morbidity and mortality. While investigating the genomic diversity of B. dolosa strains collected from an outbreak among CF patients, we previously identified fixL as a gene showing signs of strong positive selection. This gene has homology to fixL of the rhizobial FixL/FixJ two-component system...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28045404/liver-inflammation-and-fibrosis
#16
Yukinori Koyama, David A Brenner
Chronic liver inflammation leads to fibrosis and cirrhosis, which is the 12th leading cause of death in the United States. Hepatocyte steatosis is a component of metabolic syndrome and insulin resistance. Hepatic steatosis may be benign or progress to hepatocyte injury and the initiation of inflammation, which activates immune cells. While Kupffer cells are the resident macrophage in the liver, inflammatory cells such as infiltrating macrophages, T lymphocytes, neutrophils, and DCs all contribute to liver inflammation...
January 3, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28045017/protective-effects-of-intercalated-disk-protein-afadin-on-chronic-pressure-overload-induced-myocardial-damage
#17
Dimitar P Zankov, Akio Shimizu, Miki Tanaka-Okamoto, Jun Miyoshi, Hisakazu Ogita
Adhesive intercellular connections at cardiomyocyte intercalated disks (IDs) support contractile force and maintain structural integrity of the heart muscle. Disturbances of the proteins at IDs deteriorate cardiac function and morphology. An adaptor protein afadin, one of the components of adherens junctions, is expressed ubiquitously including IDs. At present, the precise role of afadin in cardiac physiology or disease is unknown. To explore this, we generated conditional knockout (cKO) mice with cardiomyocyte-targeted deletion of afadin...
January 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28039158/inhibition-of-sphingosine-1-phosphate-signaling-ameliorates-murine-nonalcoholic-steatohepatitis
#18
Amy S Mauer, Petra Hirsova, Jessica L Maiers, Vijay H Shah, Harmeet Malhi
BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a lipotoxic disorder, wherein proinflammatory lipids, such as ceramide and its derivative sphingosine 1-phosphate (S1P), contribute to macrophage-associated liver inflammation. For example, we have previously demonstrated a role for S1P in steatotic hepatocyte-derived S1P enriched extracellular vesicles in macrophage chemotaxis in vitro. Therefore, we hypothesized that FTY720, an S1P antagonist, would ameliorate NASH by inhibiting proinflammatory monocyte chemotaxis...
December 30, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28035772/deregulated-neddylation-in-liver-fibrosis
#19
Imanol Zubiete-Franco, Pablo Fernández-Tussy, Lucía Barbier-Torres, Jorge Simon, David Fernández-Ramos, Fernando Lopitz-Otsoa, Virginia Gutiérrez-de Juan, Sergio López de Davalillo, Antonio Martín Duce, Paula Iruzubieta, Daniel Taibo, Javier Crespo, Juan Caballeria, Erica Villa, Igor Aurrekoetxea, Patricia Aspichueta, Marta Varela-Rey, Shelly C Lu, José M Mato, Naiara Beraza, Teresa C Delgado, María L Martínez-Chantar
: Hepatic fibrosis is a global health problem currently without effective therapeutic approaches. Even though the ubiquitin-like posttranslational modification of neddylation, that conjugates Nedd8 (neural precursor cell expressed developmentally downregulated) to specific targets, is aberrant in many pathologies, its relevance in liver fibrosis (LF) remained unexplored. Our results show deregulated neddylation in clinical fibrosis and both in mouse bileductligation- and CCl4 -induced fibrosis...
November 7, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28034695/aberrant-lung-remodeling-in-a-mouse-model-of-surfactant-dysregulation-induced-by-modulation-of-the-abca3-gene
#20
Michael F Beers, Lars Knudsen, Yaniv Tomer, Julian Maronn, Ming Zhao, Matthias Ochs, Surafel Mulugeta
The lipid transporter, ATP binding cassette class A3 (ABCA3), plays a critical role in the biogenesis of alveolar type 2 (AT2) cell lamellar bodies (LBs). A relatively large number of mutations in the ABCA3 gene have been identified in association with diffuse parenchymal lung disease (DPLD), the most common of which is a missense mutation (valine substitution for lysine at residue 292 (ABCA3(E292V))) that leads to functional impairment of the transporter in vitro. The consequences of ABCA3(E292)(V) gene expression in vivo are unknown...
December 26, 2016: Annals of Anatomy, Anatomischer Anzeiger: Official Organ of the Anatomische Gesellschaft
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