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Mertk

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https://www.readbyqxmd.com/read/29776413/the-cxcr4-antagonist-plerixafor-amd3100-promotes-proliferation-of-ewing-sarcoma-cell-lines-in-vitro-and-activates-receptor-tyrosine-kinase-signaling
#1
Philipp Berning, Christiane Schaefer, Dagmar Clemens, Eberhard Korsching, Uta Dirksen, Jenny Potratz
BACKGROUND: The CXCR4 receptor antagonist plerixafor (AMD3100) is raising interest as an anti-cancer agent that disrupts the CXCL12-CXCR4 chemokine - receptor interaction between neoplastic cells and their microenvironment in tumor progression and metastasis. Here, we investigated plerixafor for anti-cancer activity in Ewing sarcoma, a rare and aggressive cancer of bone and soft tissues. METHODS: We used a variety of methods such as cell viability and migration assays, flow cytometry, phospho-tyrosine arrays and western blotting to determine plerixafor effects on five characterized Ewing sarcoma cell lines and a low-passage culture in vitro...
May 18, 2018: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29761388/isolation-and-identification-of-interstitial-macrophages-from-the-lungs-using-different-digestion-enzymes-and-staining-strategies
#2
Shaikh M Atif, Sophie L Gibbings, Claudia V Jakubzick
Interstitial macrophages (IMs) are present in multiple organs. Although there is limited knowledge of the unique functional role IM subtypes play, macrophages, in general, are known for their contribution in homeostatic tissue maintenance and inflammation such as clearing pathogens and debris and secreting inflammatory mediators and growth factors. IM subtypes have been identified in the heart, skin, and gut, and more recently we identified three distinct IMs in the lung. IMs express on their surface high levels of MerTK, CD64, and CD11b, with differences in CD11c, CD206, and MHC II expression, and referred to the three pulmonary IM subtypes as IM1 (CD11clo CD206+ MHCIIlo ), IM2 (CD11clo CD206+ MHCIIhi ), and IM3 (CD11chi CD206lo MHCIIhi )...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29721990/opposite-roles-of-mertk-ligands-gas6-and-protein-s-during-retinal-phagocytosis
#3
Emeline F Nandrot
MerTK is required for photoreceptor outer segment (POS) phagocytosis by retinal pigment epithelial (RPE) cells, a diurnal function essential for vision maintenance. In vivo, MerTK is stimulated at the time of the phagocytic peak through an intracellular signaling pathway. However, MerTK ligands Gas6 and Protein S are expressed in both RPE cells and photoreceptors, and at least one of them required for phagocytosis to occur. Still, their exact role in the retina was not clear until recently. This review combines results from different studies to shed the light on a tissue-specific regulation of MerTK function by its ligands...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29706963/protective-role-of-the-mer-tyrosine-kinase-via-efferocytosis-in-rheumatoid-arthritis-models
#4
Claire E J Waterborg, Silke Beermann, Mathijs G A Broeren, Miranda B Bennink, Marije I Koenders, Peter L E M van Lent, Wim B van den Berg, Peter M van der Kraan, Fons A J van de Loo
Objective: Rheumatoid arthritis (RA) is a chronic and progressive joint disease. It appears that anti-inflammatory feedback mechanisms that could restrain joint inflammation and restore homeostasis are insufficient to perform this control. In this study, we investigated the contribution of the MER tyrosine kinase-mediated anti-inflammatory response on arthritis and whether targeting MER could be a valid approach to treat RA. Methods: KRN serum transfer arthritis (KRN STA) was induced in either Mertk -deficient mice or in mice that adenovirally overexpressed Pros1 ...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29679380/a-non-myeloablative-chimeric-mouse-model-accurately-defines-microglia-and-macrophage-contribution-in-glioma
#5
Kenny Yu, A Saam Youshani, Fiona L Wilkinson, Claire O'Leary, Peter Cook, Liisi Laaniste, Aiyin Liao, Dominic Mosses, Christopher Waugh, Hannah Shorrock, Omar Pathmanaban, Andrew Macdonald, Ian Kamaly-Asl, Federico Roncaroli, Brian W Bigger
AIMS: Resident and peripherally-derived glioma associated microglia/macrophages (GAMM) play a key role in driving tumour progression, angiogenesis, invasion, and attenuating host immune responses. Differentiating these cells' origins is challenging and current pre-clinical models such as irradiation-based adoptive transfer, parabiosis and transgenic mice have limitations. We aimed to develop a novel non-myeloablative transplantation (NMT) mouse model that permits high levels of peripheral chimerism without blood-brain barrier (BBB) damage or brain infiltration prior to tumour implantation...
April 20, 2018: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/29659094/mertk-mutations-update-in-inherited-retinal-diseases
#6
Isabelle Audo, Saddek Mohand-Said, Elise Boulanger-Scemama, Xavier Zanlonghi, Christel Condroyer, Vanessa Démontant, Fiona Boyard, Aline Antonio, Cécile Méjécase, Said El Shamieh, José-Alain Sahel, Christina Zeitz
MER tyrosine kinase (MERTK) encodes a surface receptor localized at the apical membrane of the retinal pigment epithelium. It plays a critical role in photoreceptor outer segment internalization prior to phagocytosis. Mutations in MERTK have been associated with severe autosomal recessive retinal dystrophies in the RCS rat and in humans. We present here a comprehensive review of all reported MERTK disease causing variants with the associated phenotype. In addition, we provide further data and insights of a large cohort of 1195 inherited retinal dystrophies (IRD) index cases applying state-of-the-art genotyping techniques and summarize current knowledge...
April 16, 2018: Human Mutation
https://www.readbyqxmd.com/read/29555955/clinical-and-genetic-characteristics-of-251-consecutive-patients-with-macular-and-cone-cone-rod-dystrophy
#7
Johannes Birtel, Tobias Eisenberger, Martin Gliem, Philipp L Müller, Philipp Herrmann, Christian Betz, Diana Zahnleiter, Christine Neuhaus, Steffen Lenzner, Frank G Holz, Elisabeth Mangold, Hanno J Bolz, Peter Charbel Issa
Macular and cone/cone-rod dystrophies (MD/CCRD) demonstrate a broad genetic and phenotypic heterogeneity, with retinal alterations solely or predominantly involving the central retina. Targeted next-generation sequencing (NGS) is an efficient diagnostic tool for identifying mutations in patient with retinitis pigmentosa, which shows similar genetic heterogeneity. To detect the genetic causes of disease in patients with MD/CCRD, we implemented a two-tier procedure consisting of Sanger sequencing and targeted NGS including genes associated with clinically overlapping conditions...
March 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29554921/the-proto-oncogene-mer-tyrosine-kinase-is-a-novel-therapeutic-target-in-mantle-cell-lymphoma
#8
Cunzhen Shi, Xiangqun Li, Xiaogan Wang, Ning Ding, Lingyan Ping, Yunfei Shi, Lan Mi, Yumei Lai, Yuqin Song, Jun Zhu
BACKGROUND: Mantle cell lymphoma (MCL) is an incurable B cell-derived malignant tumor with a median overall survival of 4-5 years. Mer tyrosine kinase (MerTK) has been reported to be aberrantly expressed in leukemia, melanoma, and gastric cancer, and plays a pivotal role in the process of oncogenesis. This study assessed the role of MerTK in MCL for the first time. METHODS: Immunohistochemistry and western blot were performed to figure out expression of MerTK in MCL...
March 20, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29553850/mertk-mediates-stat3-kras-src-signaling-axis-for-glioma-stem-cell-maintenance
#9
Hyojin Eom, Neha Kaushik, Ki-Chun Yoo, Jin-Kyoung Shim, Munjin Kwon, Mi-Young Choi, Taeyoung Yoon, Seok-Gu Kang, Su-Jae Lee
Receptor tyrosine kinase Mer (MerTK) has been shown to be highly expressed in Glioblastoma multiforme (GBM) in comparison to its healthy counterpart and is implicated in brain tumorigenesis. Clarifying the underlying mechanism of MerTK induced invasiveness would result in novel strategies to improve patient's response to chemotherapeutics. In vitro and in vivo assays were performed to examine the functional role of cancer stem sell (CSC) maintenance in MerTK associated invasiveness. In this article, we demonstrate that apart from GBM cells, MerTK is also upregulated in GBM stem-like cells and associated with an increased infiltrative potential of brain tumors in vivo...
March 19, 2018: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29545796/macrophage-derived-protein-s-facilitates-apoptotic-polymorphonuclear-cell-clearance-by-resolution-phase-macrophages-and-supports-their-reprogramming
#10
Delphine Lumbroso, Soaad Soboh, Avi Maimon, Sagie Schif-Zuck, Amiram Ariel, Tal Burstyn-Cohen
The complete resolution of inflammation requires the uptake of apoptotic polymorphonuclear cells (PMN) by local macrophages (efferocytosis) and the consequent reprogramming of the engulfing phagocytes to reparative and pro-resolving phenotypes. The tyrosine kinase receptors TYRO3, AXL, and MERTK (collectively named TAM) are fundamental mediators in regulating inflammatory responses and efferocytosis. Protein S (PROS1) is a ligand for all TAM receptors that mediates various aspects of their activity. However, the involvement of PROS1 in the resolution of inflammation is incompletely understood...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29530050/sulforaphane-rescues-amyloid-%C3%AE-peptide-mediated-decrease-in-mertk-expression-through-its-anti-inflammatory-effect-in-human-thp-1-macrophages
#11
Kyoung A Jhang, Jin-Sun Park, Hee-Sun Kim, Young Hae Chong
BACKGROUND: Mer tyrosine kinase (MerTK) activity necessary for amyloid-stimulated phagocytosis strongly implicates that MerTK dysregulation might contribute to chronic inflammation implicated in Alzheimer's disease (AD) pathology. However, the precise mechanism involved in the regulation of MerTK expression by amyloid-β (Aβ) in proinflammatory environment has not yet been ascertained. METHODS: The objective of this study was to determine the underlying mechanism involved in Aβ-mediated decrease in MerTK expression through Aβ-mediated regulation of MerTK expression and its modulation by sulforaphane in human THP-1 macrophages challenged with Aβ1-42...
March 12, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29514053/the-role-of-tam-family-receptors-and-ligands-in-the-nervous-system-from-development-to-pathobiology
#12
REVIEW
Bridget Shafit-Zagardo, Ross C Gruber, Juwen C DuBois
Tyro3, Axl, and Mertk, referred to as the TAM family of receptor tyrosine kinases, are instrumental in maintaining cell survival and homeostasis in mammals. TAM receptors interact with multiple signaling molecules to regulate cell migration, survival, phagocytosis and clearance of metabolic products and cell debris called efferocytosis. The TAMs also function as rheostats to reduce the expression of proinflammatory molecules and prevent autoimmunity. All three TAM receptors are activated in a concentration-dependent manner by the vitamin K-dependent growth arrest-specific protein 6 (Gas6)...
March 4, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29444453/efferocytosis-in-atherosclerotic-lesions-malfunctioning-regulatory-pathways-and-control-mechanisms
#13
REVIEW
Amir Tajbakhsh, Mehdi Rezaee, Petri T Kovanen, Amirhossein Sahebkar
Atherosclerosis is a dynamic and progressive inflammatory process in the intimal layer of large and medium-sized arteries, and it is the major contributor to the atherosclerotic cardiovascular disease (ACVD), the leading cause of death worldwide. In an atherosclerotic plaque, phagocytosis of apoptotic cells occurs through an intricate process designated efferocytosis. Defective efferocytosis has emerged as a causal factor in the etiopathogenesis of atherosclerosis and its progression into overt ACVD. Both specialized phagocytes (macrophages and dendritic cells) and non-specialized cells with phagocytic capabilities (smooth muscle and endothelial cells) are involved in the efferocytotic process...
February 11, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29437494/targeted-next-generation-sequencing-reveals-a-novel-frameshift-mutation-in-the-mertk-gene-in-a-chinese-family-with-retinitis-pigmentosa
#14
Mu Yang, Shujin Li, Wenjing Liu, Yeming Yang, Lin Zhang, Shanshan Zhang, Zhilin Jiang, Zhenglin Yang, Xianjun Zhu
BACKGROUND: Retinitis pigmentosa (RP) is a group of inherited retinal diseases that result in severe progressive visual impairment. AIMS: The purpose of this article was to apply targeted next-generation sequencing (NGS) to identify the causative mutation in a Chinese RP family. METHODS: Blood samples were collected from a Chinese proband diagnosed with RP and her family members. A total of 163 genes that have been previously found to be involved in inherited retinal diseases were selected for NGS...
March 2018: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/29431645/subretinal-human-umbilical-tissue-derived-cell-transplantation-preserves-retinal-synaptic-connectivity-and-attenuates-m%C3%A3-ller-glial-reactivity
#15
Sehwon Koh, William J Chen, Nadine S Dejneka, Ian R Harris, Bin Lu, Sergey Girman, Joshua Saylor, Shaomei Wang, Cagla Eroglu
Human umbilical tissue-derived cells (hUTC or palucorcel) are currently under clinical investigation for the treatment of geographic atrophy, a late stage of macular degeneration, but how hUTC transplantation mediates vision recovery is not fully elucidated. Subretinal administration of hUTC preserves visual function in the Royal College of Surgeons (RCS) rat, a genetic model of retinal degeneration caused by Mertk loss of function. hUTC secrete synaptogenic and neurotrophic factors that improve the health and connectivity of the neural retina...
March 21, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29408905/splenic-macrophages-are-required-for-protective-innate-immunity-against-west-nile-virus
#16
Marianne A Bryan, Daniela Giordano, Kevin E Draves, Richard Green, Michael Gale, Edward A Clark
Although the spleen is a major site for West Nile virus (WNV) replication and spread, relatively little is known about which innate cells in the spleen replicate WNV, control viral dissemination, and/or prime innate and adaptive immune responses. Here we tested if splenic macrophages (MΦs) were necessary for control of WNV infection. We selectively depleted splenic MΦs, but not draining lymph node MΦs, by injecting mice intravenously with clodronate liposomes several days prior to infecting them with WNV...
2018: PloS One
https://www.readbyqxmd.com/read/29400409/axl-and-mertk-receptor-tyrosine-kinases-maintain-human-macrophage-efferocytic-capacity-in-the-presence-of-viral-triggers
#17
Aleksander M Grabiec, Anu Goenka, Mark E Fife, Toshifumi Fujimori, Tracy Hussell
The requirement to remove apoptotic cells is equally important in homeostasis and inflammatory disease. In particular, during viral infections large quantities of infected cells undergo apoptosis and need to be efficiently cleared by phagocytes to prevent secondary necrosis. Although specific roles of several apoptotic cell sensors, such as the TAM (Tyro3, Axl, MerTK) receptor family, have been characterized in mouse models, little is known about their regulation and involvement in apoptotic cell uptake (efferocytosis) by human macrophages under inflammatory conditions...
February 5, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29379818/mertk-mediated-regulation-of-myelin-phagocytosis-by-macrophages-generated-from-patients-with-ms
#18
Luke M Healy, Jeong Ho Jang, So-Yoon Won, Yun Hsuan Lin, Hanane Touil, Salman Aljarallah, Amit Bar-Or, Jack P Antel
Objective: To document functional differences between monocyte-derived macrophages (MDMs) of patients with MS and the ability of age/sex-matched healthy donor cells to phagocytose human myelin and to investigate the molecular mechanisms that underlie this. Methods: MDMs were derived from peripheral blood monocytes of 25 untreated patients with relapsing-remitting MS and secondary progressive MS and age/sex-matched healthy controls (HCs). Phagocytosis was assessed by flow cytometry using fluorescently labeled human myelin...
November 2017: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/29359540/association-between-genetic-variations-of-mertk-and-chronic-obstructive-pulmonary-disease-in-koreans
#19
Woo Jin Kim, Hyo Jin Park, Yang Ji Choi, Eun Young Kwon, Bo Min Kim, Jin Hwa Lee, Jung Hyun Chang, Jihee Lee Kang, Ji Ha Choi
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a debilitating lung disease. To date, a large number of clinical studies have been conducted to investigate the association between genetic variations and COPD. However, little is known regarding the genetic susceptibility of Koreans to this disease. MER receptor tyrosine kinase (MERTK) plays important roles in the inhibition of inflammation and in the clearance of apoptotic cells. Here, we investigated the association between genetic variations in MERTK and the development of COPD in Koreans...
February 12, 2018: Journal of Korean Medical Science
https://www.readbyqxmd.com/read/29342502/antiphospholipid-antibodies-inhibit-trophoblast-toll-like-receptor-and-inflammasome-negative-regulators
#20
Melissa J Mulla, Ingrid C Weel, Julie A Potter, Stefan M Gysler, Jane E Salmon, Maria T S Peraçoli, Carla V Rothlin, Lawrence W Chamley, Vikki M Abrahams
OBJECTIVE: Women with antiphospholipid antibodies (aPL) are at risk for pregnancy complications associated with poor placentation and placental inflammation. While these antibodies are heterogeneous, some anti-β2 GPI antibodies can activate human first trimester trophoblast TLR4 and NLRP3. The objective of this study was to determine the role of negative regulators of TLR and inflammasome function in aPL-induced trophoblast inflammation. METHODS: Human trophoblast cells were treated with or without anti-β2 GPI aPL or control IgG in the presence or absence of the common TAM receptor ligand, GAS6, or the autophagy inducer, rapamycin...
January 17, 2018: Arthritis & Rheumatology
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