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https://www.readbyqxmd.com/read/28634207/dazed-and-confused-from-infection
#1
Wei Wong
TNF-α produced by circulating CX3CR1(high) monocytes causes the problems that infected individuals have with learning and remembering.
June 20, 2017: Science Signaling
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
#2
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
#3
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/28615357/donor-pulmonary-intravascular-nonclassical-monocytes-recruit-recipient-neutrophils-and-mediate-primary-lung-allograft-dysfunction
#4
Zhikun Zheng, Stephen Chiu, Mahzad Akbarpour, Haiying Sun, Paul A Reyfman, Kishore R Anekalla, Hiam Abdala-Valencia, Daphne Edgren, Wenjun Li, Daniel Kreisel, Farida V Korobova, Ramiro Fernandez, Alexandra McQuattie-Pimentel, Zheng J Zhang, Harris Perlman, Alexander V Misharin, G R Scott Budinger, Ankit Bharat
Primary graft dysfunction is the predominant driver of mortality and graft loss after lung transplantation. Recruitment of neutrophils as a result of ischemia-reperfusion injury is thought to cause primary graft dysfunction; however, the mechanisms that regulate neutrophil influx into the injured lung are incompletely understood. We found that donor-derived intravascular nonclassical monocytes (NCMs) are retained in human and murine donor lungs used in transplantation and can be visualized at sites of endothelial injury after reperfusion...
June 14, 2017: Science Translational Medicine
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
#5
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
#6
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/28596556/indoxyl-sulfate-is-mediated-immune-dysfunction-provokes-endothelial-damage-in-patients-with-end-stage-renal-disease-esrd
#7
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/28558818/microrna-101a-regulates-microglial-morphology-and-inflammation
#8
Reiko Saika, Hiroshi Sakuma, Daisuke Noto, Shuhei Yamaguchi, Takashi Yamamura, Sachiko Miyake
BACKGROUND: Microglia, as well as other tissue-resident macrophages, arise from yolk sac progenitors. Thus, it is likely that the central nervous system environment is critical for the acquisition of a distinct microglial phenotype. Several microRNAs that are enriched in the brain play crucial roles in brain development and may also play a role in the differentiation of microglia. METHODS: To track the differentiation of hematopoietic cells into microglia, lineage-negative bone marrow cells were co-cultured with astrocytes in the absence or presence of microRNAs or their inhibitors...
May 30, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28552674/enrichment-increases-hippocampal-neurogenesis-independent-of-blood-monocyte-derived-microglia-presence-following-high-dose-total-body-irradiation
#9
Marc J Ruitenberg, Julia Wells, Perry F Bartlett, Alan R Harvey, Jana Vukovic
Birth of new neurons in the hippocampus persists in the brain of adult mammals and critically underpins optimal learning and memory. The process of adult neurogenesis is significantly reduced following brain irradiation and this correlates with impaired cognitive function. In this study, we aimed to compare the long-term effects of two environmental paradigms (i.e. enriched environment and exercise) on adult neurogenesis following high-dose (10Gy) total body irradiation. When housed in standard (sedentary) conditions, irradiated mice revealed a long-lasting (up to at least 4 months) deficit in neurogenesis in the granule cell layer of the dentate gyrus, the region that harbors the neurogenic niche...
May 24, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28540528/sema3a-promotes-the-resolution-of-cardiac-inflammation-after-myocardial-infarction
#10
Marieke Rienks, Paolo Carai, Nicole Bitsch, Mark Schellings, Maarten Vanhaverbeke, Johan Verjans, Ilona Cuijpers, Stephane Heymans, Anna Papageorgiou
Optimal healing after myocardial infarction requires not only the induction of inflammation, but also its timely resolution. In patients, 30 days post myocardial infarction, circulating monocytes have increased expression of Semaphorin3A (Sema3A) as compared to directly after admission. This increased expression coincides with increased expression of Cx3CR1-a marker of non-classical monocytes that are important for immune resolution hence proper wound healing. In mice, the expression of Sema3A also increases in response to myocardial ischemia being expressed by infiltrating leukocytes...
July 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28528700/directed-differentiation-of-human-pluripotent-stem-cells-to-microglia
#11
Panagiotis Douvaras, Bruce Sun, Minghui Wang, Ilya Kruglikov, Gregory Lallos, Matthew Zimmer, Cecile Terrenoire, Bin Zhang, Sam Gandy, Eric Schadt, Donald O Freytes, Scott Noggle, Valentina Fossati
Microglia, the immune cells of the brain, are crucial to proper development and maintenance of the CNS, and their involvement in numerous neurological disorders is increasingly being recognized. To improve our understanding of human microglial biology, we devised a chemically defined protocol to generate human microglia from pluripotent stem cells. Myeloid progenitors expressing CD14/CX3CR1 were generated within 30 days of differentiation from both embryonic and induced pluripotent stem cells (iPSCs). Further differentiation of the progenitors resulted in ramified microglia with highly motile processes, expressing typical microglial markers...
June 6, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28522896/shear-stress-counteracts-endothelial-cx3cl1-induction-and-monocytic-cell-adhesion
#12
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/28504723/cx3cr1-monocytes-modulate-learning-and-learning-dependent-dendritic-spine-remodeling-via-tnf-%C3%AE
#13
Juan Mauricio Garré, Hernandez Moura Silva, Juan J Lafaille, Guang Yang
Impaired learning and cognitive function often occurs during systemic infection or inflammation. Although activation of the innate immune system has been linked to the behavioral and cognitive effects that are associated with infection, the underlying mechanisms remain poorly understood. Here we mimicked viral immune activation with poly(I:C), a synthetic analog of double-stranded RNA, and longitudinally imaged postsynaptic dendritic spines of layer V pyramidal neurons in the mouse primary motor cortex using two-photon microscopy...
June 2017: Nature Medicine
https://www.readbyqxmd.com/read/28501330/virus-entry-and-replication-in-the-brain-precedes-blood-brain-barrier-disruption-during-intranasal-alphavirus-infection
#14
Matthew D Cain, Hamid Salimi, Yongfeng Gong, Lihua Yang, Samantha L Hamilton, James R Heffernan, Jianghui Hou, Mark J Miller, Robyn S Klein
Viral infections of the central nervous system (CNS) are often associated with blood-brain barrier (BBB) disruption, yet the impact of virus replication and immune cell recruitment on BBB integrity are incompletely understood. Using two-photon microscopy, we demonstrate that Venezuelan equine encephalitis virus (VEEV) strain TC83-GFP, a GFP expressing, attenuated strain with a G3A mutation within the 5' UTR that is associated with increased sensitivity to type I interferons (IFNs), does not directly impact BBB permeability...
July 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28487961/influence-of-aspirin-on-the-cx3cl1-cx3cr1-signaling-pathway-in-acute-pulmonary-embolism
#15
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/28472653/migrating-interneurons-secrete-fractalkine-to-promote-oligodendrocyte-formation-in-the-developing-mammalian-brain
#16
Anastassia Voronova, Scott A Yuzwa, Beatrix S Wang, Siraj Zahr, Charvi Syal, Jing Wang, David R Kaplan, Freda D Miller
During development, newborn interneurons migrate throughout the embryonic brain. Here, we provide evidence that these interneurons act in a paracrine fashion to regulate developmental oligodendrocyte formation. Specifically, we show that medial ganglionic eminence (MGE) interneurons secrete factors that promote genesis of oligodendrocytes from glially biased cortical precursors in culture. Moreover, when MGE interneurons are genetically ablated in vivo prior to their migration, this causes a deficit in cortical oligodendrogenesis...
May 3, 2017: Neuron
https://www.readbyqxmd.com/read/28464004/vitamin-d-deficiency-is-associated-with-il-6-levels-and-monocyte-activation-in-hiv-infected-persons
#17
Maura Manion, Katherine Huppler Hullsiek, Eleanor M P Wilson, Frank Rhame, Erna Kojic, David Gibson, John Hammer, Pragna Patel, John T Brooks, Jason V Baker, Irini Sereti
BACKGROUND: Immune activation plays a key role in HIV pathogenesis. Markers of inflammation have been associated with vitamin D deficiency in the general population. Studies have also demonstrated associations of vitamin D deficiency with increased risk of HIV progression and death. The relationship between persistent inflammation and immune activation during chronic HIV infection and vitamin D deficiency remains unclear. METHODS: Cryopreserved specimens were analyzed from 663 participants at the time of enrollment from the Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy (SUN Study) from 2004 to 2006...
2017: PloS One
https://www.readbyqxmd.com/read/28462835/synthesis-and-preliminary-biological-evaluation-of-11-c-methyl-2-amino-5-benzylthio-thiazolo-4-5-d-pyrimidin-7-yl-d-leucinate-for-the-fractalkine-receptor-cx3cr1
#18
Mingzhang Gao, Min Wang, Jill A Meyer, Jonathan S Peters, Hamideh Zarrinmayeh, Paul R Territo, Gary D Hutchins, Qi-Huang Zheng
The reference standard methyl (2-amino-5-(benzylthio)thiazolo[4,5-d]pyrimidin-7-yl)-d-leucinate (5) and its precursor 2-amino-5-(benzylthio)thiazolo[4,5-d]pyrimidin-7-yl)-d-leucine (6) were synthesized from 6-amino-2-mercaptopyrimidin-4-ol and BnBr with overall chemical yield 7% in five steps and 4% in six steps, respectively. The target tracer [(11)C]methyl (2-amino-5-(benzylthio)thiazolo[4,5-d]pyrimidin-7-yl)-d-leucinate ([(11)C]5) was prepared from the acid precursor with [(11)C]CH3OTf through O-[(11)C]methylation and isolated by HPLC combined with SPE in 40-50% radiochemical yield, based on [(11)C]CO2 and decay corrected to end of bombardment (EOB)...
June 15, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28459435/brown-adipose-tissue-macrophages-control-tissue-innervation-and-homeostatic-energy-expenditure
#19
Yochai Wolf, Sigalit Boura-Halfon, Nina Cortese, Zhana Haimon, Hadas Sar Shalom, Yael Kuperman, Vyacheslav Kalchenko, Alexander Brandis, Eyal David, Yifat Segal-Hayoun, Louise Chappell-Maor, Avraham Yaron, Steffen Jung
Tissue macrophages provide immunological defense and contribute to the establishment and maintenance of tissue homeostasis. Here we used constitutive and inducible mutagenesis to delete the nuclear transcription regulator Mecp2 in macrophages. Mice that lacked the gene encoding Mecp2, which is associated with Rett syndrome, in macrophages did not show signs of neurodevelopmental disorder but displayed spontaneous obesity, which was linked to impaired function of brown adipose tissue (BAT). Specifically, mutagenesis of a BAT-resident Cx3Cr1(+) macrophage subpopulation compromised homeostatic thermogenesis but not acute, cold-induced thermogenesis...
June 2017: Nature Immunology
https://www.readbyqxmd.com/read/28459434/mice-deficient-in-nrros-show-abnormal-microglial-development-and-neurological-disorders
#20
Kit Wong, Rajkumar Noubade, Paolo Manzanillo, Naruhisa Ota, Oded Foreman, Jason A Hackney, Brad A Friedman, Rajita Pappu, Kimberly Scearce-Levie, Wenjun Ouyang
Microglia and other tissue-resident macrophages within the central nervous system (CNS) have essential roles in neural development, inflammation and homeostasis. However, the molecular pathways underlying their development and function remain poorly understood. Here we report that mice deficient in NRROS, a myeloid-expressed transmembrane protein in the endoplasmic reticulum, develop spontaneous neurological disorders. NRROS-deficient (Nrros(-/-)) mice show defects in motor functions and die before 6 months of age...
June 2017: Nature Immunology
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