keyword
MENU ▼
Read by QxMD icon Read
search

Mertk

keyword
https://www.readbyqxmd.com/read/29118755/apoptotic-cells-induced-signaling-for-immune-homeostasis-in-macrophages-and-dendritic-cells
#1
REVIEW
Uriel Trahtemberg, Dror Mevorach
Inefficient and abnormal clearance of apoptotic cells (efferocytosis) contributes to systemic autoimmune disease in humans and mice, and inefficient chromosomal DNA degradation by DNAse II leads to systemic polyarthritis and a cytokine storm. By contrast, efficient clearance allows immune homeostasis, generally leads to a non-inflammatory state for both macrophages and dendritic cells (DCs), and contributes to maintenance of peripheral tolerance. As many as 3 × 10(8) cells undergo apoptosis every hour in our bodies, and one of the primary "eat me" signals expressed by apoptotic cells is phosphatidylserine (PtdSer)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29116131/context-dependent-compensation-among-phosphatidylserine-recognition-receptors
#2
Kristen K Penberthy, Claudia Rival, Laura S Shankman, Michael H Raymond, Jianye Zhang, Justin S A Perry, Chang Sup Lee, Claudia Z Han, Suna Onengut-Gumuscu, Krzysztof Palczewski, Jeffrey J Lysiak, Kodi S Ravichandran
Phagocytes express multiple phosphatidylserine (PtdSer) receptors that recognize apoptotic cells. It is unknown whether these receptors are interchangeable or if they play unique roles during cell clearance. Loss of the PtdSer receptor Mertk is associated with apoptotic corpse accumulation in the testes and degeneration of photoreceptors in the eye. Both phenotypes are linked to impaired phagocytosis by specialized phagocytes: Sertoli cells and the retinal pigmented epithelium (RPE). Here, we overexpressed the PtdSer receptor BAI1 in mice lacking MerTK (Mertk (-/-) Bai1 (Tg) ) to evaluate PtdSer receptor compensation in vivo...
November 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29109727/dexamethasone-and-monophosphoryl-lipid-a-induce-a-distinctive-profile-on-monocyte-derived-dendritic-cells-through-transcriptional-modulation-of-genes-associated-with-essential-processes-of-the-immune-response
#3
Paulina A García-González, Katina Schinnerling, Alejandro Sepúlveda-Gutiérrez, Jaxaira Maggi, Ahmed M Mehdi, Hendrik J Nel, Bárbara Pesce, Milton L Larrondo, Octavio Aravena, María C Molina, Diego Catalán, Ranjeny Thomas, Ricardo A Verdugo, Juan C Aguillón
There is growing interest in the use of tolerogenic dendritic cells (tolDCs) as a potential target for immunotherapy. However, the molecular bases that drive the differentiation of monocyte-derived DCs (moDCs) toward a tolerogenic state are still poorly understood. Here, we studied the transcriptional profile of moDCs from healthy subjects, modulated with dexamethasone (Dex) and activated with monophosphoryl lipid A (MPLA), referred to as Dex-modulated and MPLA-activated DCs (DM-DCs), as an approach to identify molecular regulators and pathways associated with the induction of tolerogenic properties in tolDCs...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29101300/pharmacoproteomic-characterisation-of-human-colon-and-rectal-cancer
#4
Martin Frejno, Riccardo Zenezini Chiozzi, Mathias Wilhelm, Heiner Koch, Runsheng Zheng, Susan Klaeger, Benjamin Ruprecht, Chen Meng, Karl Kramer, Anna Jarzab, Stephanie Heinzlmeir, Elaine Johnstone, Enric Domingo, David Kerr, Moritz Jesinghaus, Julia Slotta-Huspenina, Wilko Weichert, Stefan Knapp, Stephan M Feller, Bernhard Kuster
Most molecular cancer therapies act on protein targets but data on the proteome status of patients and cellular models for proteome-guided pre-clinical drug sensitivity studies are only beginning to emerge. Here, we profiled the proteomes of 65 colorectal cancer (CRC) cell lines to a depth of > 10,000 proteins using mass spectrometry. Integration with proteomes of 90 CRC patients and matched transcriptomics data defined integrated CRC subtypes, highlighting cell lines representative of each tumour subtype...
November 3, 2017: Molecular Systems Biology
https://www.readbyqxmd.com/read/29056937/cd14-cells-with-the-phenotype-of-infiltrated-monocytes-consist-of-distinct-populations-characterized-by-anti-inflammatory-as-well-as-pro-inflammatory-activity-in-gouty-arthritis
#5
Ji Hye Jeong, Seokchan Hong, Oh Chan Kwon, Byeongzu Ghang, Inseok Hwang, Yong-Gil Kim, Chang-Keun Lee, Bin Yoo
It has been suggested that inflammasome-mediated IL-1β production in monocytic cells is responsible for the acute inflammatory response in gouty arthritis. However, phenotypical and functional analyses of monocytes during gouty arthritis have yet to be conducted. Therefore, we investigated the characteristics of monocytes/macrophages in the synovial fluid cells of patients with acute gout. The number and frequency of monocytes/macrophages in the synovial fluid mononuclear cells (SFMCs) of patients was examined...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29050198/mtorc1-autophagy-regulated-mertk-in-mutant-brafv600-melanoma-with-acquired-resistance-to-braf-inhibition
#6
Gongda Xue, Reto Kohler, Fengyuan Tang, Debby Hynx, Yuhua Wang, Francesca Orso, Vincent Prêtre, Reto Ritschard, Petra Hirschmann, Peter Cron, Tim Roloff, Reinhard Dummer, Mario Mandalà, Sandrine Bichet, Christel Genoud, Alexandra G Meyer, Manuele G Muraro, Giulio C Spagnoli, Daniela Taverna, Curzio Rüegg, Taha Merghoub, Daniela Massi, Huifang Tang, Mitchell P Levesque, Stephan Dirnhofer, Alfred Zippelius, Brian A Hemmings, Andreas Wicki
BRAF inhibitors (BRAFi) and the combination therapy of BRAF and MEK inhibitors (MEKi) were recently approved for therapy of metastatic melanomas harbouring the oncogenic BRAFV600 mutation. Although these therapies have shown pronounced therapeutic efficacy, the limited durability of the response indicates an acquired drug resistance that still remains mechanistically poorly understood at the molecular level. We conducted transcriptome gene profiling in BRAFi-treated melanoma cells and identified that Mer tyrosine kinase (MerTK) is specifically upregulated...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29045015/the-small-molecule-mertk-inhibitor-unc2025-decreases-platelet-activation-and-prevents-thrombosis
#7
Brian R Branchford, Timothy J Stalker, Luke Law, Gilbert Acevedo, Susan Sather, Christine Brzezinski, Katina M Wilson, Katherine Minson, Alisa B Lee-Sherick, Pavel Davizon-Castillo, Christopher Ng, Weihe Zhang, Keith B Neeves, Steven R Lentz, Xiaodong Wang, Stephen V Frye, H Shelton Earp, Deborah DeRyckere, Lawrence F Brass, Douglas K Graham, Jorge A Di Paola
BACKGROUND: Gas6 signals through the TAM (TYRO-3, AXL, MERTK) receptor family mediating platelet activation and thrombus formation via activation of the aggregate-stabilizing αIIb β3 integrin. OBJECTIVE: Here we describe anti-thrombotic effects mediated by UNC2025, a small molecule MERTK tyrosine kinase inhibitor. METHODS: MERTK phosphorylation and downstream signaling were assessed by immunoblot. Light transmission aggregometry, flow cytometry, and microfluidic analysis were used to evaluate the impact of MERTK inhibition on platelet activation and stability of aggregate formation in vitro...
October 17, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28988713/otx2-genetically-modified-retinal-pigment-epithelial-cells-rescue-photoreceptors-after-transplantation
#8
Christo Kole, Laurence Klipfel, Ying Yang, Vanessa Ferracane, Frederic Blond, Sacha Reichman, Géraldine Millet-Puel, Emmanuelle Clérin, Najate Aït-Ali, Delphine Pagan, Hawa Camara, Marie-Noëlle Delyfer, Emeline F Nandrot, Jose-Alain Sahel, Olivier Goureau, Thierry Léveillard
Inherited retinal degenerations are blinding diseases characterized by the loss of photoreceptors. Their extreme genetic heterogeneity complicates treatment by gene therapy. This has motivated broader strategies for transplantation of healthy retinal pigmented epithelium to protect photoreceptors independently of the gene causing the disease. The limited clinical benefit for visual function reported up to now is mainly due to dedifferentiation of the transplanted cells that undergo an epithelial-mesenchymal transition...
September 8, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28972541/camkii%C3%AE-suppresses-an-efferocytosis-pathway-in-macrophages-and-promotes-atherosclerotic-plaque-necrosis
#9
Amanda C Doran, Lale Ozcan, Bishuang Cai, Ze Zheng, Gabrielle Fredman, Christina C Rymond, Bernhard Dorweiler, Judith C Sluimer, Joanne Hsieh, George Kuriakose, Alan R Tall, Ira Tabas
Atherosclerosis is the underlying etiology of cardiovascular disease, the leading cause of death worldwide. Atherosclerosis is a heterogeneous disease in which only a small fraction of lesions lead to heart attack, stroke, or sudden cardiac death. A distinct type of plaque containing large necrotic cores with thin fibrous caps often precipitates these acute events. Here, we show that Ca2+/calmodulin-dependent protein kinase γ (CaMKIIγ) in macrophages plays a major role in the development of necrotic, thin-capped plaques...
November 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28935638/phagocytosis-of-microparticles-by-alveolar-macrophages-during-acute-lung-injury-requires-mertk
#10
Michael P Mohning, Stacey M Thomas, Lea Barthel, Kara J Mould, Alexandra L McCubbrey, S Courtney Frasch, Donna Bratton, Peter M Henson, William J Janssen
Microparticles are a newly recognized class of mediators in the pathophysiology of lung inflammation and injury, but little is known about the factors that regulate their accumulation and clearance. The primary objective of our study was to determine whether alveolar macrophages engulf microparticles and to elucidate the mechanisms by which this occurs. Alveolar microparticles were quantified in bronchoalveolar fluid of mice with lung injury induced by LPS and hydrochloric acid. Microparticle numbers were greatest at the peak of inflammation and declined as inflammation resolved...
September 21, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28925029/loss-of-gas6-and-axl-signaling-results-in-extensive-axonal-damage-motor-deficits-prolonged-neuroinflammation-and-less-remyelination-following-cuprizone-exposure
#11
Alex K Ray, Juwen C DuBois, Ross C Gruber, Hillary M Guzik, Maria E Gulinello, Geoffrey Perumal, Cedric Raine, Lauren Kozakiewicz, Julie Williamson, Bridget Shafit-Zagardo
The TAM (Tyro3, Axl, and MerTK) family of receptor tyrosine kinases (RTKs) and their ligands, Gas6 and ProS1, are important for innate immune responses and central nervous system (CNS) homeostasis. While only Gas6 directly activates Axl, ProS1 activation of Tyro3/MerTK can indirectly activate Axl through receptor heterodimerization. Therefore, we generated Gas6(-/-) Axl(-/-) double knockout (DKO) mice to specifically examine the contribution of this signaling axis while retaining ProS1 signaling through Tyro3 and MerTK...
December 2017: Glia
https://www.readbyqxmd.com/read/28916522/viral-infection-sensitizes-human-fetal-membranes-to-bacterial-lipopolysaccharide-by-mertk-inhibition-and-inflammasome-activation
#12
Sarah N Cross, Julie A Potter, Paulomi Aldo, Ja Young Kwon, Mary Pitruzzello, Mancy Tong, Seth Guller, Carla V Rothlin, Gil Mor, Vikki M Abrahams
Chorioamnionitis, premature rupture of fetal membranes (FMs), and subsequent preterm birth are associated with local infection and inflammation, particularly IL-1β production. Although bacterial infections are commonly identified, other microorganisms may play a role in the pathogenesis. Because viral pandemics, such as influenza, Ebola, and Zika, are becoming more common, and pregnant women are at increased risk for associated complications, this study evaluated the impact that viral infection had on human FM innate immune responses...
October 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28874532/schwann-cells-use-tam-receptor-mediated-phagocytosis-in-addition-to-autophagy-to-clear-myelin-in-a-mouse-model-of-nerve-injury
#13
Amanda Brosius Lutz, Won-Suk Chung, Steven A Sloan, Glenn A Carson, Lu Zhou, Emilie Lovelett, Sean Posada, J Bradley Zuchero, Ben A Barres
Ineffective myelin debris clearance is a major factor contributing to the poor regenerative ability of the central nervous system. In stark contrast, rapid clearance of myelin debris from the injured peripheral nervous system (PNS) is one of the keys to this system's remarkable regenerative capacity, but the molecular mechanisms driving PNS myelin clearance are incompletely understood. We set out to discover new pathways of PNS myelin clearance to identify novel strategies for activating myelin clearance in the injured central nervous system, where myelin debris is not cleared efficiently...
September 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28860151/myeloid-receptor-cd36-is-required-for-early-phagocytosis-of-myocardial-infarcts-and-induction-of-nr4a1-dependent-mechanisms-of-cardiac-repair
#14
Shirley Dehn, Edward B Thorp
Phagocytosis after myocardial infarction (MI) is a prerequisite to cardiac repair. Recruited monocytes clear necrotic cardiomyocytes and differentiate into cardiac macrophages. Some studies have linked apoptotic cell receptors on cardiac macrophages to tissue repair; however, the contribution of precursor monocyte phagocytic receptors, which are the first to interact with the cardiac parenchyma, is unclear. The scavenger receptor cluster of differentiation (CD)36 protein was detected on cardiac Ly6cHI monocytes, and bone marrow-derived Cd36 was essential for both early phagocytosis of dying cardiomyocytes and for smaller infarct sizes in female and male mice after permanent coronary ligation...
August 31, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28851810/mertk-cleavage-on-resident-cardiac-macrophages-compromises-repair-after-myocardial-ischemia-reperfusion-injury
#15
Matthew DeBerge, Xin Yi Yeap, Shirley Dehn, Shuang Zhang, Lubov Grigoryeva, Sol Misener, Daniel Procissi, Xin Zhou, Daniel C Lee, William A Muller, Xunrong Luo, Carla Rothlin, Ira Tabas, Edward B Thorp
RATIONALE: Clinical benefits of reperfusion after myocardial infarction are offset by maladaptive innate immune cell function, and therapeutic interventions are lacking. OBJECTIVE: We sought to test the significance of phagocytic clearance by resident and recruited phagocytes after myocardial ischemia reperfusion. METHODS AND RESULTS: In humans, we discovered that clinical reperfusion after myocardial infarction led to significant elevation of the soluble form of MerTK (myeloid-epithelial-reproductive tyrosine kinase; ie, soluble MER), a critical biomarker of compromised phagocytosis by innate macrophages...
September 29, 2017: Circulation Research
https://www.readbyqxmd.com/read/28839093/imaging-the-emergence-and-natural-progression-of-spontaneous-autoimmune-diabetes
#16
James F Mohan, Rainer H Kohler, Jonathan A Hill, Ralph Weissleder, Diane Mathis, Christophe Benoist
Type 1 diabetes in the nonobese diabetic mouse stems from an infiltration of the pancreatic islets by a mixed population of immunocytes, which results in the impairment and eventual destruction of insulin-producing β-cells. Little is known about the dynamics of lymphocyte movement in the pancreas during disease progression. Using advanced intravital imaging approaches and newly created reporter mice (Flt3-BFP2, Mertk-GFP-DTR, Cd4-tdTomato, Cd8a-tdTomato), we show that the autoimmune process initiates first with a T cell infiltration into the islets, where they have restricted mobility but reside and are activated in apposition to CX3CR1(+) macrophages...
September 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28813472/an-intronic-line-1-insertion-in-mertk-is-strongly-associated-with-retinopathy-in-swedish-vallhund-dogs
#17
Richard Everson, Louise Pettitt, Oliver P Forman, Olivia Dower-Tylee, Bryan McLaughlin, Saija Ahonen, Maria Kaukonen, András M Komáromy, Hannes Lohi, Cathryn S Mellersh, Jane Sansom, Sally L Ricketts
The domestic dog segregates a significant number of inherited progressive retinal diseases, several of which mirror human retinal diseases and which are collectively termed progressive retinal atrophy (PRA). In 2014, a novel form of PRA was reported in the Swedish Vallhund breed, and the disease was mapped to canine chromosome 17. The causal mutation was not identified, but expression analyses of the retinas of affected Vallhunds demonstrated a 6-fold increased expression of the MERTK gene compared to unaffected dogs...
2017: PloS One
https://www.readbyqxmd.com/read/28801233/t-cell-zone-resident-macrophages-silently-dispose-of-apoptotic-cells-in-the-lymph-node
#18
Myriam Baratin, Léa Simon, Audrey Jorquera, Clément Ghigo, Doulaye Dembele, Jonathan Nowak, Rebecca Gentek, Stephan Wienert, Frederick Klauschen, Bernard Malissen, Marc Dalod, Marc Bajénoff
In lymph nodes (LNs), dendritic cells (DCs) are thought to dispose of apoptotic cells, a function pertaining to macrophages in other tissues. We found that a population of CX3CR1(+) MERTK(+) cells located in the T cell zone of LNs, previously identified as DCs, are efferocytic macrophages. Lineage-tracing experiments and shield chimeras indicated that these T zone macrophages (TZM) are long-lived macrophages seeded in utero and slowly replaced by blood monocytes after birth. Imaging the LNs of mice in which TZM and DCs express different fluorescent proteins revealed that TZM-and not DCs-act as the only professional scavengers, clearing apoptotic cells in the LN T cell zone in a CX3CR1-dependent manner...
August 15, 2017: Immunity
https://www.readbyqxmd.com/read/28751473/identification-of-the-macrophage-specific-promoter-signature-in-fantom5-mouse-embryo-developmental-time-course-data
#19
Kim M Summers, David A Hume
The FANTOM5 consortium used cap analysis of gene expression (CAGE) to analyze the time course of gene expression over development from 11 days postcoitum (dpc) to adult in 16 developing organs and the whole body of the mouse. Every tissue in the body contains a large number of resident macrophages that initially infiltrate the embryo from the yolk sac. These cells contribute to organogenesis, and their functions diversify during development as they acquire tissue-specific adaptations. In each of the FANTOM5 time courses, the expression of known macrophage-specific genes, including CSF1 receptor (Csf1r), epidermal growth factor-like module-containing mucin-like hormone receptor-like 1 (Emr1), and mer receptor tyrosine kinase (Mertk), was readily detectable and increased with time...
October 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28727830/the-receptor-tyrosine-kinase-axl-promotes-migration-and-invasion-in-colorectal-cancer
#20
Diana J Uribe, Edward K Mandell, Adam Watson, Jesse D Martinez, Jonathan A Leighton, Sourav Ghosh, Carla V Rothlin
The receptor tyrosine kinases (RTKs) TYRO3, AXL and MERTK (TAM) have well-described oncogenic functions in a number of cancers. Notwithstanding, TAM RTKs are also potent and indispensable inhibitors of inflammation. The combined deletion of Axl and Mertk in mice enhances chronic inflammation and autoimmunity, including increased inflammation in the gut and colitis-associated cancer. On the other hand, deletion of Tyro3 increases the risk of allergic responses. Therefore, the indiscriminate inhibition of these TAM RTKs could result in undesirable immunological diseases...
2017: PloS One
keyword
keyword
16604
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"