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https://www.readbyqxmd.com/read/28727998/enrichment-of-endogenous-fractalkine-and-anti-inflammatory-cells-via-aptamer-functionalized-hydrogels
#1
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...
July 10, 2017: Biomaterials
https://www.readbyqxmd.com/read/28717419/platelet-extracellular-vesicles-induce-a-pro-inflammatory-smooth-muscle-cell-phenotype
#2
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
#3
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
#4
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...
July 10, 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
#5
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
#6
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
#7
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
#8
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
https://www.readbyqxmd.com/read/28654911/radial-artery-intima-media-thickness-regresses-after-secondary-prevention-interventions-in-patients-post-acute-coronary-syndrome-and-is-associated-with-cardiac-and-kidney-biomarkers
#9
Damilola D Adingupu, Helena U Westergren, Santosh Dahgam, Ann-Cathrine Jönsson-Rylander, Juuso Blomster, Per Albertsson, Elmir Omerovic, Sara Svedlund, Li-Ming Gan
BACKGROUND: Radial artery intima-media thickness (rIMT) measured by ultra-high-resolution ultrasound is associated with increased cardiovascular risk and predicts outcomes. We performed non-invasive high-resolution ultrasound of the radial artery to investigate vascular changes in subjects presenting with acute coronary syndrome (ACS) and who had undergone percutaneous coronary intervention (PCI). PURPOSE: In the present work, we aimed to follow rIMT change over time post-acute coronary syndrome as a tool to monitor potential response to intensified medical therapy...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28641299/monocyte-subsets-are-differentially-lost-from-the-circulation-during-acute-inflammation-induced-by-human-experimental-endotoxemia
#10
Tamar Tak, Roger van Groenendael, Peter Pickkers, Leo Koenderman
Three human monocyte subsets are recognized with different functions in the immune system: CD14++/CD16- classical monocytes (CM), CD14++/CD16+ intermediate monocytes (IM) and CD14+/CD16++ non-classical monocytes (NCM). Increased IM and NCM percentages have been reported under inflammatory conditions, yet little is known about monocyte subsets at the onset of inflammation. The human endotoxemia model is uniquely capable of studying the first phases of acute inflammation induced by intravenous injection of 2 ng/kg bodyweight lipopolysaccharide (LPS) into healthy volunteers...
June 23, 2017: Journal of Innate Immunity
https://www.readbyqxmd.com/read/28624392/role-of-fractalkine-cx3cr1-signaling-pathway-in-the-recovery-of-neurological-function-after-early-ischemic-stroke-in-a-rat-model
#11
Yan-Zhi Liu, Chun Wang, Qian Wang, Yong-Zhong Lin, Yu-Song Ge, Dong-Mei Li, Geng-Sheng Mao
This study aims to explore the role of fractalkine/CX3C chemokine receptor 1 (CX3CR1) signaling pathway in the recovery of neurological functioning after an early ischemic stroke in rats. After establishment of permanent middle cerebral artery occlusion (pMCAO) models, 50 rats were divided into blank, sham, model, positive control and CX3CR1 inhibitor groups. Neurological impairment, walking and grip abilities, and cortical and hippocampal infarctions were evaluated by Zea Longa scoring criterion, beam-walking assay and grip strength test, and diffusion-weighted magnetic resonance imaging...
June 14, 2017: Life Sciences
https://www.readbyqxmd.com/read/28619710/heme-oxygenase-1-production-by-intestinal-cx3cr1-macrophages-helps-to-resolve-inflammation-and-prevents-carcinogenesis
#12
Giulia Marelli, Marco Erreni, Achille Anselmo, Valentina Taverniti, Simone Guglielmetti, Alberto Mantovani, Paola Allavena
CX3CR1(+) macrophages in the intestinal lamina propria contribute to gut homeostasis through the immunomodulatory interleukin IL-10, but there is little knowledge on how these cells or the CX3CR1 receptor may affect colorectal carcinogenesis. In this study, we show that CX3CR1-deficient mice fail to resolve gut inflammation despite high production of IL-10 and have increased colitis and adenomatous polyps in chemical and genetic models of colon carcinogenesis. Mechanistically, CX3CL1-mediated engagement of the CX3CR1 receptor induced upregulation of hemoxygenase-1 (HMOX-1), an antioxidant and anti-inflammatory enzyme...
June 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28612319/involvement-of-nf-%C3%AE%C2%BAb-and-the-cx3cr1-signaling-network-in-mechanical-allodynia-induced-by-tetanic-sciatic-stimulation
#13
Zhe-Chen Wang, Li-Hong Li, Chao Bian, Liu Yang, Ning Lv, Yu-Qiu Zhang
Tetanic stimulation of the sciatic nerve (TSS) triggers long-term potentiation in the dorsal horn of the spinal cord and long-lasting pain hypersensitivity. CX3CL1-CX3CR1 signaling is an important pathway in neuronal-microglial activation. Nuclear factor κB (NF-κB) is a key signal transduction molecule that regulates neuroinflammation and neuropathic pain. Here, we set out to determine whether and how NF-κB and CX3CR1 are involved in the mechanism underlying the pathological changes induced by TSS. After unilateral TSS, significant bilateral mechanical allodynia was induced, as assessed by the von Frey test...
June 13, 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/28612258/downregulated-glia-interplay-and-increased-mirna-155-as-promising-markers-to-track-als-at-an%C3%A2-early-stage
#14
Carolina Cunha, Catarina Santos, Cátia Gomes, Adelaide Fernandes, Alexandra Marçal Correia, Ana Maria Sebastião, Ana Rita Vaz, Dora Brites
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of unknown cause. Absence of specific targets and biomarkers compromise the development of new therapeutic strategies and of innovative tools to stratify patients and assess their responses to treatment. Here, we investigate changes in neuroprotective-neuroinflammatory actions in the spinal cord of SOD1 (G93A) mice, at presymptomatic and symptomatic stages to identify stage-specific biomarkers and potential targets. Results showed that in the presymptomatic stage, there are alterations in both astrocytes and microglia, which comprise decreased expression of GFAP and S100B and upregulation of GLT-1, as well as reduced expression of CD11b, M2-phenotype markers, and a set of inflammatory mediators...
June 13, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28600292/adam10-interacting-tetraspanins-tspan5-and-tspan17-regulate-ve-cadherin-expression-and-promote-t-lymphocyte-transmigration
#15
Jasmeet S Reyat, Myriam Chimen, Peter J Noy, Justyna Szyroka, G Ed Rainger, Michael G Tomlinson
The recruitment of blood leukocytes across the endothelium to sites of tissue infection is central to inflammation, but also promotes chronic inflammatory diseases. A disintegrin and metalloproteinase 10 (ADAM10) is a ubiquitous transmembrane molecular scissor that is implicated in leukocyte transmigration by proteolytically cleaving its endothelial substrates. These include VE-cadherin, a homotypic adhesion molecule that regulates endothelial barrier function, and transmembrane chemokines CX3CL1 and CXCL16, which have receptors on leukocytes...
July 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28596556/indoxyl-sulfate-is-mediated-immune-dysfunction-provokes-endothelial-damage-in-patients-with-end-stage-renal-disease-esrd
#16
Hee Young Kim, Tae-Hyun Yoo, Yuri Hwang, Ga Hye Lee, Bonah Kim, Jiyeon Jang, Hee Tae Yu, Min Chang Kim, Joo-Youn Cho, Chan Joo Lee, Hyeon Chang Kim, Sungha Park, Won-Woo Lee
Progressive renal failure causes uremia-related immune dysfunction, which features a chronic inflammatory milieu. Given the central role of end-stage renal disease (ESRD)-related immune dysfunction in the pathogenesis of cardiovascular diseases (CVDs), much attention has been focused on how uremic toxins affect cellular immunity and the mechanisms underlying pathogenesis of atherosclerosis in ESRD patients. Here, we investigated the characteristics of monocytes and CD4(+) T cells in ESRD patients and the immune responses induced by indoxyl sulfate (IS), a key uremic toxin, in order to explore the pathogenic effects of these cells on vascular endothelial cells...
June 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28569153/aberrant-monocyte-responses-predict-and-characterize-dengue-virus-infection-in-individuals-with-severe-disease
#17
Yean K Yong, Hong Y Tan, Soe Hui Jen, Esaki M Shankar, Santha K Natkunam, Jameela Sathar, Rishya Manikam, Shamala D Sekaran
BACKGROUND: Currently, several assays can diagnose acute dengue infection. However, none of these assays can predict the severity of the disease. Biomarkers that predicts the likelihood that a dengue patient will develop a severe form of the disease could permit more efficient patient triage and allows better supportive care for the individual in need, especially during dengue outbreaks. METHODS: We measured 20 plasma markers i.e. IFN-γ, IL-10, granzyme-B, CX3CL1, IP-10, RANTES, CXCL8, CXCL6, VCAM, ICAM, VEGF, HGF, sCD25, IL-18, LBP, sCD14, sCD163, MIF, MCP-1 and MIP-1β in 141 dengue patients in over 230 specimens and correlate the levels of these plasma markers with the development of dengue without warning signs (DWS-), dengue with warning signs (DWS+) and severe dengue (SD)...
May 31, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28522896/shear-stress-counteracts-endothelial-cx3cl1-induction-and-monocytic-cell-adhesion
#18
Aaron Babendreyer, Lisa Molls, Daniela Dreymueller, Stefan Uhlig, Andreas Ludwig
Flow conditions critically regulate endothelial cell functions in the vasculature. Reduced shear stress resulting from disturbed blood flow can drive the development of vascular inflammatory lesions. On endothelial cells, the transmembrane chemokine CX3CL1/fractalkine promotes vascular inflammation by functioning as a surface-expressed adhesion molecule and by becoming released as soluble chemoattractant for monocytic cells expressing the receptor CX3CR1. Here, we report that endothelial cells from human artery, vein, or microvasculature constitutively express CX3CL1 when cultured under static conditions...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28487961/influence-of-aspirin-on-the-cx3cl1-cx3cr1-signaling-pathway-in-acute-pulmonary-embolism
#19
Zhirong Zhang, Weiji Yang, Rongbiao Ying, Ying Shi, Huifang Jiang, Danli Cai, Jing Kuang, Ruhui Yang, Lingcong Wang
The present study aimed to explore the influence of aspirin on the CX3CL1/CX3CR1 signaling pathway in acute pulmonary embolism (APE) in rats. Our previous study found that CX3CL1/CX3CR1 was increased in APE. However, the effect of this signaling pathway on APE remains unclear. CX3CL1-shRNA adenovirus and CX3CL1-overexpression vector were constructed. Male Sprague-Dawley rats were randomly divided into 9 groups (n=10): normal group (group N), sham operation group (group Sham), sham operation + aspirin group (group ASP), model group (group M), model + ASP group (group M+A), model + shRNA group (group M+SH), sham operation + CX3CL1-overexpression vector group (group Sham+Cx3), model + ASP + shRNA group (group M+A+SH), and model + ASP + CX3CL1-overexpression vector group (group M+A+CX3)...
April 26, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28470428/genome-wide-dna-methylation-analysis-of-articular-chondrocytes-identifies-traf1-ctgf-and-cx3cl1-genes-as-hypomethylated-in-osteoarthritis
#20
Like Zhao, Qian Wang, Chunmei Zhang, Cibo Huang
The aim of this study is to identify osteoarthritis (OA)-associated differentially methylated genes in human articular chondrocytes from patients with OA. DNA methylation profiling of articular chondrocytes from OA patients, rheumatoid arthritis (RA) patients, and controls was performed, and candidate genes were chosen for validation of gene demethylation status. The mRNA expression levels of candidate genes in chondrocytes were detected by real-time quantitative PCR. Chondrocytes from OA and RA group were treated with 5-Aza-2-deoxycytidine (5-Aza), and then the mRNA expression levels were detected...
May 3, 2017: Clinical Rheumatology
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