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CX3CL1

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https://www.readbyqxmd.com/read/28810923/the-chemokine-fractalkine-cx3cl1-attenuates-h2o2-induced-demyelination-in-cerebellar-slices
#1
Sinead A O'Sullivan, Kumlesh K Dev
BACKGROUND: Fractalkine/CX3CR1 signalling has been implicated in many neurodegenerative and neurological diseases of the central nervous system (CNS). This signalling pathway plays an important role in regulating reactive oxygen species (ROS), as well as itself being altered in conditions of oxidative stress. Here, we investigated the effects of recombinant fractalkine (rCX3CL1) in models of hydrogen peroxide (H2O2)-induced demyelination and astrocyte toxicity, within organotypic cerebellar slice cultures...
August 15, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28810892/absence-of-cx3cr1-impairs-the-internalization-of-tau-by-microglia
#2
Marta Bolós, María Llorens-Martín, Juan Ramón Perea, Jerónimo Jurado-Arjona, Alberto Rábano, Félix Hernández, Jesús Avila
BACKGROUND: Extracellular Tau is toxic for neighboring cells, and it contributes to the progression of AD. The CX3CL1/CX3CR1 axis is an important neuron/microglia communication mechanism. METHODS: We studied Tau clearance by microglia both in vitro (microglia primary cultures treated with Cy5-Tau, affinity chromatography to study the binding of Tau to CX3CR1, and Tau-CX3CL1 competition assays) and in vivo (stereotaxic injection of Cy5-Tau into WT and CX3CR1(-/-) mice)...
August 15, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28800592/cx3cr1-knockout-aggravates-coxsackievirus-b3-induced-myocarditis
#3
Irene Müller, Kathleen Pappritz, Konstantinos Savvatis, Kerstin Puhl, Fengquan Dong, Muhammad El-Shafeey, Nazha Hamdani, Isabell Hamann, Michel Noutsias, Carmen Infante-Duarte, Wolfgang A Linke, Sophie Van Linthout, Carsten Tschöpe
Studies on inflammatory disorders elucidated the pivotal role of the CX3CL1/CX3CR1 axis with respect to the pathophysiology and diseases progression. Coxsackievirus B3 (CVB3)-induced myocarditis is associated with severe cardiac inflammation, which may progress to heart failure. We therefore investigated the influence of CX3CR1 ablation in the model of acute myocarditis, which was induced by inoculation with 5x105 plaque forming units of CVB3 (Nancy strain) in either CX3CR1-/- or C57BL6/j (WT) mice. Seven days after infection, myocardial inflammation, remodeling, and titin expression and phosphorylation were examined by immunohistochemistry, real-time PCR and Pro-Q diamond stain...
2017: PloS One
https://www.readbyqxmd.com/read/28780154/chemokines-as-new-inflammatory-players-in-the-pathogenesis-of-epilepsy
#4
REVIEW
Chiara Cerri, Matteo Caleo, Yuri Bozzi
A large series of clinical and experimental studies supports a link between inflammation and epilepsy, indicating that inflammatory processes within the brain are important contributors to seizure recurrence and precipitation. Systemic inflammation can precipitate seizures in children suffering from epileptic encephalopathies, and hallmarks of a chronic inflammatory state have been found in patients with temporal lobe epilepsy. Research performed on animal models of epilepsy further corroborates the idea that seizures upregulate inflammatory mediators, which in turn may enhance brain excitability and neuronal degeneration...
July 27, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28776289/spinal-cx3cl1-cx3cr1-may-not-directly-participate-in-the-development-of-morphine-tolerance-in-rats
#5
Yawen Peng, Genhua Guo, Bin Shu, Daiqiang Liu, Peng Su, Xuming Zhang, Feng Gao
CX3CL1 (fractalkine), the sole member of chemokine CX3C family, is implicated in inflammatory and neuropathic pain via activating its receptor CX3CR1 on neural cells in spinal cord. However, it has not been fully elucidated whether CX3CL1 or CX3CR1 contributes to the development of morphine tolerance. In this study, we found that chronic morphine exposure did not alter the expressions of CX3CL1 and CX3CR1 in spinal cord. And neither exogenous CX3CL1 nor CX3CR1 inhibitor could affect the development of morphine tolerance...
August 3, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28754850/the-regulation-of-hydroxysteroid-17%C3%AE-dehydrogenase-type-1-and-2-gene-expression-in-breast-cancer-cell-lines-by-estradiol-dihydrotestosterone-micrornas-and-genes-related-to-breast-cancer
#6
Erik Hilborn, Olle Stål, Andrey Alexeyenko, Agneta Jansson
AIM: To investigate the influence of estrogen, androgen, microRNAs, and genes implicated in breast cancer on the expression of HSD17B1 and HSD17B2. MATERIALS: Breast cancer cell lines ZR-75-1, MCF7, T47D, SK-BR-3, and the immortalized epithelial cell line MCF10A were used. Cells were treated either with estradiol or dihydrotestosterone for 6, 24, 48 hours, or 7 days or treated with miRNAs or siRNAs predicted to influence HSD17B expression Results and discussion...
July 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28754163/choroid-plexus-cerebrospinal-fluid-route-for-monocyte-derived-macrophages-after-stroke
#7
Ruimin Ge, Daniel Tornero, Masao Hirota, Emanuela Monni, Cecilia Laterza, Olle Lindvall, Zaal Kokaia
BACKGROUND: Choroid plexus (CP) supports the entry of monocyte-derived macrophages (MDMs) to the central nervous system in animal models of traumatic brain injury, spinal cord injury, and Alzheimer's disease. Whether the CP is involved in the recruitment of MDMs to the injured brain after ischemic stroke is unknown. METHODS: Adult male C57BL/6 mice were subjected to focal cortical ischemia by permanent occlusion of the distal branch of the right middle cerebral artery...
July 28, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28751644/minimal-hepatic-encephalopathy-is-associated-with-expansion-and-activation-of-cd-4-cd28-th22-and-tfh-and-b-lymphocytes
#8
Alba Mangas-Losada, Raquel García-García, Amparo Urios, Desamparados Escudero-García, Joan Tosca, Remedios Giner-Durán, Miguel Angel Serra, Carmina Montoliu, Vicente Felipo
Peripheral inflammation acts synergistically with hyperammonemia in inducing neurological alterations in cirrhotic patients with minimal hepatic encephalopathy (MHE). We hypothesized that appearance of MHE would be associated to some specific qualitative change in peripheral inflammation. The aim of this work was to characterize the changes in peripheral inflammation associated to appearance of MHE. We analyzed it by immunophenotyping and cytokine profile analysis, in cirrhotic patients without or with MHE and controls...
July 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28747747/involvement-of-monocyte-subsets-in-the-immunopathology-of-giant-cell-arteritis
#9
Yannick van Sleen, Qi Wang, Kornelis S M van der Geest, Johanna Westra, Wayel H Abdulahad, Peter Heeringa, Annemieke M H Boots, Elisabeth Brouwer
Monocytes/macrophages are critical in systemic and local inflammation in giant cell arteritis (GCA) and possibly in clinically overlapping polymyalgia rheumatica (PMR). Therefore, we aimed to understand the contribution of monocyte subsets and the CX3CR1-CX3CL1 and CCR2-CCL2 migratory pathways, to the pathology of GCA. Peripheral blood monocytes were enumerated in samples from newly-diagnosed, untreated GCA and PMR patients and after prednisone-induced remission. The distribution of classical (CD14(bright)CD16(neg)) and the more pro-inflammatory, intermediate (CD14(bright)CD16+) and non-classical (CD14(dim)CD16+) monocyte subsets was analysed by flow cytometry...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28746417/immunological-and-inflammatory-mapping-of-vascularized-composite-allograft-rejection-processes-in-a-rat-model
#10
Or Friedman, Narin Carmel, Meirav Sela, Ameen Abu Jabal, Amir Inbal, Moshe Ben Hamou, Yakov Krelin, Eyal Gur, Nir Shani
BACKGROUND: Hand and face vascularized composite allotransplantation (VCA) is an evolving and challenging field with great opportunities. During VCA, massive surgical damage is inflicted on both donor and recipient tissues, which may contribute to the high VCA rejection rates. To segregate between the damage-induced and rejection phase of post-VCA responses, we compared responses occurring up to 5 days following syngeneic versus allogeneic vascularized groin flap transplantations, culminating in transplant acceptance or rejection, respectively...
2017: PloS One
https://www.readbyqxmd.com/read/28739588/n-terminal-pyroglutamate-formation-in-cx3cl1-is-essential-for-its-full-biologic-activity
#11
Astrid Kehlen, Monique Haegele, Livia Böhme, Holger Cynis, Torsten Hoffmann, Hans-Ulrich Demuth
CX3CL1 is the unique member of the CX3C chemokine family and mediates both adhesion and cell migration in inflammatory processes. Frequently, the activity of chemokines depends on a modified N-terminus as described for the N-terminus of CCL2 modified to a pyroglutamate (pGlu-) residue by glutaminyl cyclase activity. Here, we assess the role of the pGlu-modified residue of the CX3CL1 chemokine domain in human endothelial and smooth muscle cells. For the first time, we demonstrated using mass spectrometry that glutaminyl cyclase (QC, QPCT ) or its isoenzyme isoQC ( QPCTL ) catalyse the formation of N-terminal modified pGlu-CX3CL1...
July 24, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28732748/controlling-the-pro-inflammatory-function-of-6-sulfo-lacnac-slan-dendritic-cells-with-dimethylfumarate
#12
Stephanie Oehrl, Florina Olaru, Anja Kunze, Michael Maas, Silvia Pezer, Marc Schmitz, Knut Schäkel
BACKROUND: The fumaric acid ester (FAE) dimethylfumarate (DMF) is a small molecule immunomodulator successfully used for the treatment of psoriasis and multiple sclerosis (MS). DMF is thought to inhibit pathogenic immune responses with Th17/Th1T cells, and IL-23/IL-12 producing dendritic cells (DCs). 6-sulfo LacNAc expressing dendritic cells (slanDCs) are a human pro-inflammatory cell type found frequently among the infiltrating leukocytes in skin lesions of psoriasis and brain lesions of MS...
June 24, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28727998/enrichment-of-endogenous-fractalkine-and-anti-inflammatory-cells-via-aptamer-functionalized-hydrogels
#13
Syed Faaiz Enam, Jack R Krieger, Tarun Saxena, Brian E Watts, Claire E Olingy, Edward A Botchwey, Ravi V Bellamkonda
Early recruitment of non-classical monocytes and their macrophage derivatives is associated with augmented tissue repair and improved integration of biomaterial constructs. A promising therapeutic approach to recruit these subpopulations is by elevating local concentrations of chemoattractants such as fractalkine (FKN, CX3CL1). However, delivering recombinant or purified proteins is not ideal due to their short half-lives, suboptimal efficacy, immunogenic potential, batch variabilities, and cost. Here we report an approach to enrich endogenous FKN, obviating the need for delivery of exogenous proteins...
October 2017: Biomaterials
https://www.readbyqxmd.com/read/28717419/platelet-extracellular-vesicles-induce-a-pro-inflammatory-smooth-muscle-cell-phenotype
#14
Tanja Vajen, Birke J Benedikter, Alexandra C A Heinzmann, Elena M Vasina, Yvonne Henskens, Martin Parsons, Patricia B Maguire, Frank R Stassen, Johan W M Heemskerk, Leon J Schurgers, Rory R Koenen
Extracellular vesicles (EVs) are mediators of cell communication during health and disease, and abundantly released by platelets upon activation or during ageing. Platelet EVs exert modulatory effects on immune and vascular cells. Platelet EVs may modulate the function of vascular smooth muscle cells (SMC). Platelet EVs were isolated from platelet-rich plasma and incubated with SMC in order to assess binding, proliferation, migration and pro-inflammatory phenotype of the cells. Platelet EVs firmly bound to resting SMC through the platelet integrin αIIbβ3, while binding also occurred in a CX3CL1-CX3CR1-dependent manner after cytokine stimulation...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28713392/il-15-harnesses-pro-inflammatory-function-of-temra-cd8-in-kidney-transplant-recipients
#15
Gaëlle Tilly, Tra-My Doan-Ngoc, Michelle Yap, Aurélie Caristan, Lola Jacquemont, Richard Danger, Marion Cadoux, Sarah Bruneau, Magali Giral, Pierrick Guerif, Bryan Nicol, Alexandra Garcia, David-Axel Laplaud, Sophie Brouard, Claire Pecqueur Hellman, Nicolas Degauque
The involvement of TEMRA CD8 is evident in a large array of immunological conditions ranging from auto- to allo-immunity. Nevertheless, the factors leading to their accumulation and activation remain ill-defined and, efficient therapeutics to control their inflammatory response is lacking. Here, we show that IL-15-stimulated TEMRA from kidney-transplant (KT) recipients promote inflammation by inducing the expression of CX3CL1 by endothelial cells in an IFN-γ- and TNF-α-dependent manner. The responsiveness of TEMRA to IL-15 is not restricted to chronic stimulation, as TEMRA from healthy volunteers respond earlier and faster when compared to effector memory (EM)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28691930/ly6clo-monocytes-drive-immunosuppression-and-confer-resistance-to-anti-vegfr2-cancer-therapy
#16
Keehoon Jung, Takahiro Heishi, Omar F Khan, Piotr S Kowalski, Joao Incio, Nuh N Rahbari, Euiheon Chung, Jeffrey W Clark, Christopher G Willett, Andrew D Luster, Seok Hyun Yun, Robert Langer, Daniel G Anderson, Timothy P Padera, Rakesh K Jain, Dai Fukumura
Current anti-VEGF therapies for colorectal cancer (CRC) provide limited survival benefit, as tumors rapidly develop resistance to these agents. Here, we have uncovered an immunosuppressive role for nonclassical Ly6Clo monocytes that mediates resistance to anti-VEGFR2 treatment. We found that the chemokine CX3CL1 was upregulated in both human and murine tumors following VEGF signaling blockade, resulting in recruitment of CX3CR1+Ly6Clo monocytes into the tumor. We also found that treatment with VEGFA reduced expression of CX3CL1 in endothelial cells in vitro...
August 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28681650/safety-pharmacokinetics-and-efficacy-of-e6011-an-antifractalkine-monoclonal-antibody-in-a-first-in-patient-phase-1-2-study-on-rheumatoid-arthritis
#17
Yoshiya Tanaka, Tsutomu Takeuchi, Hisanori Umehara, Toshihiro Nanki, Nobuyuki Yasuda, Fumitoshi Tago, Makoto Kawakubo, Yasumi Kitahara, Seiichiro Hojo, Tetsu Kawano, Toshio Imai
OBJECTIVE: Fractalkine (CX3CL1/FKN) is a chemokine that regulates chemotaxis and adhesion of CX3C chemokine receptor 1 (CX3CR1)-expressing inflammatory cells. We conducted the first phase 1/2, open-label, multiple ascending dose study of E6011, a humanized anti-FKN monoclonal antibody, in Japanese rheumatoid arthritis (RA) patients (clinicaltrial.gov identifier: NCT02196558). METHODS: Active RA patients with an inadequate response or intolerance to methotrexate or tumor necrosis factor (TNF) inhibitor received E6011 at week 0, 1, 2, and thereafter every 2 weeks for 12 weeks...
July 6, 2017: Modern Rheumatology
https://www.readbyqxmd.com/read/28677664/allergenic-proteases-cleave-the-chemokine-cx3cl1-directly-from-the-surface-of-airway-epithelium-and-augment-the-effect-of-rhinovirus
#18
M Loxham, D E Smart, N J Bedke, N P Smithers, I Filippi, C Blume, E J Swindle, K Tariq, P H Howarth, S T Holgate, D E Davies
CX3CL1 has been implicated in allergen-induced airway CD4(+) T-lymphocyte recruitment in asthma. As epidemiological evidence supports a viral infection-allergen synergy in asthma exacerbations, we postulated that rhinovirus (RV) infection in the presence of allergen augments epithelial CX3CL1 release. Fully differentiated primary bronchial epithelial cultures were pretreated apically with house dust mite (HDM) extract and infected with rhinovirus-16 (RV16). CX3CL1 was measured by enzyme-linked immunosorbent assay and western blotting, and shedding mechanisms assessed using inhibitors, protease-activated receptor-2 (PAR-2) agonist, and recombinant CX3CL1-expressing HEK293T cells...
July 5, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28659168/gene-expression-profiles-and-signaling-mechanisms-in-%C3%AE-2b-adrenoceptor-evoked-proliferation-of-vascular-smooth-muscle-cells
#19
Anna Huhtinen, Vesa Hongisto, Asta Laiho, Eliisa Löyttyniemi, Dirk Pijnenburg, Mika Scheinin
BACKGROUND: α2-adrenoceptors are important regulators of vascular tone and blood pressure. Regulation of cell proliferation is a less well investigated consequence of α2-adrenoceptor activation. We have previously shown that α2B-adrenoceptor activation stimulates proliferation of vascular smooth muscle cells (VSMCs). This may be important for blood vessel development and plasticity and for the pathology and therapeutics of cardiovascular disorders. The underlying cellular mechanisms have remained mostly unknown...
June 28, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28655972/high-glucose-level-disturbs-the-resveratrol-evoked-curtailment-of-cx3cl1-cx3cr1-signaling-in-human-placental-circulation
#20
Dariusz Szukiewicz, Michal Pyzlak, Grzegorz Szewczyk, Aleksandra Stangret, Seweryn Trojanowski, Michal Bachanek, Wojciech Braksator, Jaroslaw Wejman
Hyperglycemia-induced hyperactivity of chemokine CX3CL1 (fractalkine) occurs in the human placenta. Anti-inflammatory/antioxidant activities of resveratrol (3,5,4'-trihydroxy-trans-stilbene) are related to the modulation of chemokine CX3CL1 and its receptor, CX3CR1, signaling pathways. We examined the influence of high glucose (25 mmol/L glucose; HG group; N = 36) on resveratrol-mediated effects on CX3CL1 and TNF-α production by the placental lobule, CX3CR1 expression and contents of CX3CR1, TNF-α receptor 1 (TNFR1), and NF-κB proteins in placental tissue...
2017: Mediators of Inflammation
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