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https://www.readbyqxmd.com/read/27926736/structure-of-cc-chemokine-receptor-2-with-orthosteric-and-allosteric-antagonists
#1
Yi Zheng, Ling Qin, Natalia V Ortiz Zacarías, Henk de Vries, Gye Won Han, Martin Gustavsson, Marta Dabros, Chunxia Zhao, Robert J Cherney, Percy Carter, Dean Stamos, Ruben Abagyan, Vadim Cherezov, Raymond C Stevens, Adriaan P IJzerman, Laura H Heitman, Andrew Tebben, Irina Kufareva, Tracy M Handel
CC chemokine receptor 2 (CCR2) is one of 19 members of the chemokine receptor subfamily of human class A G-protein-coupled receptors. CCR2 is expressed on monocytes, immature dendritic cells, and T-cell subpopulations, and mediates their migration towards endogenous CC chemokine ligands such as CCL2 (ref. 1). CCR2 and its ligands are implicated in numerous inflammatory and neurodegenerative diseases including atherosclerosis, multiple sclerosis, asthma, neuropathic pain, and diabetic nephropathy, as well as cancer...
December 7, 2016: Nature
https://www.readbyqxmd.com/read/27918885/mutant-ccl2-protein-coating-mitigates-wear-particle-induced-bone-loss-in-a-murine-continuous-polyethylene-infusion-model
#2
Akira Nabeshima, Jukka Pajarinen, Tzu-Hua Lin, Xinyi Jiang, Emmanuel Gibon, Luis A Córdova, Florence Loi, Laura Lu, Eemeli Jämsen, Kensuke Egashira, Fan Yang, Zhenyu Yao, Stuart B Goodman
Wear particle-induced osteolysis limits the long-term survivorship of total joint replacement (TJR). Monocyte/macrophages are the key cells of this adverse reaction. Monocyte Chemoattractant Protein-1 (MCP-1/CCL2) is the most important chemokine regulating trafficking of monocyte/macrophages in particle-induced inflammation. 7ND recombinant protein is a mutant of CCL2 that inhibits CCL2 signaling. We have recently developed a layer-by-layer (LBL) coating platform on implant surfaces that can release biologically active 7ND...
November 24, 2016: Biomaterials
https://www.readbyqxmd.com/read/27918831/induction-of-chemokine-secretion-and-monocyte-migration-by-human-choroidal-melanocytes-in-response-to-proinflammatory-cytokines
#3
Tina Jehs, Carsten Faber, Maja S Udsen, Martine J Jager, Simon J Clark, Mogens H Nissen
Purpose: To determine to which extent inflammatory cytokines affect chemokine secretion by primary human choroidal melanocytes (HCMs), their capacity to attract monocytes, and whether HCMs are able to influence the proliferation of activated T cells. Methods: Primary cultures of HCMs were established from eyes of 13 donors. Human choroidal melanocytes were stimulated with IFN-γ and TNF-α or with supernatant from activated T cells (T-cell-conditioned media [TCM])...
December 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27913426/depletion-of-circulating-monocytes-suppresses-il-17-and-hmgb1-expression-in-mice-with-lps-induced-acute-lung-injury
#4
Zhilong Jiang, Qianlin Zhou, Chenlin Gu, Dandan Li, Lei Zhu
Acute lung injury/Acute Respiratory distress syndrome (ALI/ARDS) is an important cause of mortality in critically ill patients. Macrophages play an important role in the pathogenesis of ALI/ARDS. To investigate the role and underlying mechanisms of circulating monocytes and resident alveolar macrophages (AMs) in ALI/ARDS, we depleted circulating monocytes and AMs by clodronate-loaded liposome (CL) in lipopolysaccharide (LPS)-induced ALI/ARDS mouse model. Our results indicated that depletion of circulating monocytes by intravenous (i...
December 2, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27910818/histomorphometric-and-transcriptome-evaluation-of-early-healing-bone-treated-with-a-novel-human-particulate-dentin-powder
#5
Yu-Chih Huang, Wei-Zhen Lew, Sheng-Wei Feng, Wei-Yi Lai, Yoshimitsu Abiko, Haw-Ming Huang
Human particulate dentin (HPD) shows potential as an alternative bone grafting material. However, the mechanism of bone healing at the molecular level after grafting with HPD is unclear. This study assessed the histological and global gene expression of bone tissues grafted with HPD. The HPD was prepared to 250-500 µm in size. X-ray diffraction (XRD) and energy dispersive x-ray spectroscopy (EDX) were performed to confirm the crystal structure, organic compound residues, and surface morphology, respectively...
December 2, 2016: Biomedical Materials
https://www.readbyqxmd.com/read/27909248/regulation-of-chemokine-receptor-ccr2-recycling-by-filamin-a-phosphorylation
#6
Mònica Pons, Ismael Izquierdo, Mireia Andreu-Carbó, Georgina Garrido, Jesús Planagumà, Olivia Muriel, M Isabel Geli, Anna M Aragay
Proper endosomal trafficking of ligand-activated G protein-coupled receptors (GPCRs) is essential to spatiotemporally tune their physiological responses. For the monocyte chemoattractant receptor 2 (CCR2B), endocytic recycling is important to sustain monocyte migration; while filamin A (FLNa) is essential for CCL2-induced monocyte migration. Here, we analyze the role of FLNa in the trafficking of CCR2B along the endocytic pathway. In FLNa knockdown cells, activated CCR2B accumulated in enlarged EEA-1-positive endosomes, which exhibited slow movement and fast fluorescence recovery, suggesting an imbalance between receptor entry and exit rates...
December 1, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27902740/extensive-characterization-and-comparison-of-endothelial-cells-derived-from-dermis-and-adipose-tissue-potential-use-in-tissue-engineering
#7
Hanneke N Monsuur, Ester M Weijers, Frank B Niessen, Amit Gefen, Pieter Koolwijk, Susan Gibbs, Lenie J van den Broek
Tissue-engineered constructs need to become quickly vascularized in order to ensure graft take. One way of achieving this is to incorporate endothelial cells (EC) into the construct. The adipose tissue stromal vascular fraction (adipose-SVF) might provide an alternative source for endothelial cells as adipose tissue can easily be obtained by liposuction. Since adipose-EC are now gaining more interest in tissue engineering, we aimed to extensively characterize endothelial cells from adipose tissue (adipose-EC) and compare them with endothelial cells from dermis (dermal-EC)...
2016: PloS One
https://www.readbyqxmd.com/read/27902351/protective-role-of-cx3cr1-signaling-in-resident-cells-of-the-central-nervous-system-during-experimental-herpes-simplex-virus-encephalitis
#8
Rafik Menasria, Coraline Canivet, Jocelyne Piret, Jean Gosselin, Guy Boivin
CX3CR1 is an important chemokine receptor expressed on the surface of microglia and blood leukocytes including monocytes. Signaling through this receptor influences the immune activity of microglia and monocytes trafficking into the central nervous system (CNS) in several neurological diseases. During experimental herpes simplex virus 1 (HSV-1) encephalitis (HSE), CX3CR1 deficiency has been reported to exacerbate the outcome of the disease. However, the precise contribution of CX3CR1 expressed in resident cells of the CNS or peripheral monocytes in protection against HSE remains unclear...
November 30, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27901204/response-of-a-co-culture-model-of-epithelial-cells-and-gingival-fibroblasts-to-zoledronic-acid
#9
Fernanda Gonçalves Basso, Diana Gabriela Soares, Taisa Nogueira Pansani, Ana Paula Silveira Turrioni, Débora Lopes Scheffel, Josimeri Hebling, Carlos Alberto de Souza Costa
Osteonecrosis of the jaw is an adverse effect of bisphosphonates. While the etiopathogenesis of this condition has been investigated, the interactions and effects of bisphosphonates on oral mucosa cells remain unclear. It is hypothesized that cell culture models, such as co-culture or three-dimensional cell culture models, can provide valuable insight. Therefore, the aim of this study was to evaluate the effects of zoledronic acid (ZA) on epithelial cells and gingival fibroblasts in a co-culture model. Briefly, epithelial cells were seeded on transwell inserts and gingival fibroblasts were seeded in the lower well of 24-well plates...
November 28, 2016: Brazilian Oral Research
https://www.readbyqxmd.com/read/27900586/role-of-prolactin-in-promotion-of-immune-cell-migration-into-the-mammary-gland
#10
Riva Dill, Ameae M Walker
Immune cells in the mammary gland play a number of important roles, including protection against infection during lactation and, after passing into milk, modulation of offspring immunity. However, little is known about the mechanism of recruitment of immune cells to the lactating gland in the absence of infection. Given the importance of prolactin to other aspects of lactation, we hypothesized it would also play a role in immune cell recruitment. Prolactin treatment of adult female mice for a period equivalent to pregnancy and the first week of lactation increased immune cell flux through the mammary gland, as reflected in the number of immune cells in mammary gland-draining, but not other lymph nodes...
November 29, 2016: Journal of Mammary Gland Biology and Neoplasia
https://www.readbyqxmd.com/read/27895698/combinations-of-bio-active-dietary-constituents-affect-human-white-adipocyte-function-in-vitro
#11
Ines Warnke, Johan W E Jocken, Rotraut Schoop, Christine Toepfer, Regina Goralczyk, Joseph Schwager
BACKGROUND: Specific bio-active dietary compounds modulate numerous metabolic processes in adipose tissue (AT), including pre-adipocyte proliferation and differentiation. AT dysfunction, rather than an increased fat mass per se, is strongly associated with the development of insulin resistance and is characterized by impaired adipogenesis, hypertrophic adipocytes, inflammation, and impairments in substrate metabolism. A better understanding of mechanisms underlying AT dysfunction may provide new strategies for the treatment of obesity-associated metabolic diseases...
2016: Nutrition & Metabolism
https://www.readbyqxmd.com/read/27895167/pgi2-controls-pulmonary-nk-cells-that-prevent-airway-sensitization-to-house-dust-mite-allergen
#12
Bryan Simons, Maria E Ferrini, Sophia Carvalho, David J P Bassett, Zeina Jaffar, Kevan Roberts
In allergic asthma, inhalation of airborne allergens such as the house dust mite (HDM) effectively activates both innate and adaptive immunity in the lung mucosa. To determine the role of the eicosanoid PGI2 and its receptor IP during allergic airway sensitization, HDM responses in mice lacking a functional IP receptor (i.e., PGI2 IP receptor-deficient [IP(-/-)]) were compared with wild type (WT) mice. Surprisingly, IP(-/-) mice had increased numbers of pulmonary CD3(-)NK1.1(+)Ly49b(+) NK cells producing IFN-γ that was inversely associated with the number of type 2 innate lymphoid cells (ILC2s) expressing IL-33Rα and IL-13 compared with WT animals...
November 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27894935/brief-report-stage-specific-differences-in-secretory-profile-of-mesenchymal-stromal-cells-mscs-subjected-to-early-vs-late-stage-oa-synovial-fluid
#13
Alejandro Gómez-Aristizábal, Anirudh Sharma, Mohsen A Bakooshli, Mohit Kapoor, Penney M Gilbert, Sowmya Viswanathan, Rajiv Gandhi
OBJECTIVE: Although, mesenchymal stromal cells (MSCs) are being clinically investigated for their use in osteoarthritis (OA), it is unclear whether their postulated therapeutic properties are equally effective in the early- and late-stages of OA. In this study we investigated MSC cytokine secretion post-exposure to synovial fluid (SF), obtained from early-vs. late-stage knee OA patients to justify a potential patient stratification strategy to maximize MSC-mediated treatment effects. METHOD: Subjects were recruited and categorized into early- [Kellgren-Lawrence (KL) grade I/II, n = 12] and late-stage (KL-III/IV, n = 12) knee OA groups...
November 25, 2016: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/27894396/ellagic-acid-ameliorates-cuprizone-induced-acute-cns-inflammation-via-restriction-of-microgliosis-and-down-regulation-of-ccl2-and-ccl3-pro-inflammatory-chemokines
#14
N Sanadgol, F Golab, A Mostafaie, M Mehdizadeh, M Abdollahi, M Sharifzadeh, H Ravan
Ellagic acid (EA) is a natural phenol antioxidant with various therapeutic activities. However, the efficacy of EA has not been examined in neuro-inflammatory conditions. Microglia making the innate immune system of the central nervous system (CNS) and are imperative cellular mediators of neuro-inflammatory processes. In this study, neuro-protective effects of EA on cuprizone (Cup)-induced acute CNS inflammation evaluated. C57BL/6J mice were fed with chow containing 0.2 % Cup for 3 weeks to induce acute neuro-inflammation predominantly in the corpus callosum (CC)...
October 31, 2016: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/27889626/absence-of-kynurenine-3-monooxygenase-reduces-mortality-of-acute-viral-myocarditis-in-mice
#15
Hisako Kubo, Masato Hoshi, Akihiro Mouri, Chieko Tashita, Yasuko Yamamoto, Toshitaka Nabeshima, Kuniaki Saito
Infection of the encephalomyocarditis virus (EMCV) in mice is an established model for viral myocarditis. Previously, we have demonstrated that indoleamine 2,3-dioxygenase (IDO), an L-tryptophan - kynurenine pathway (KP) enzyme, affects acute viral myocarditis. However, the roles of KP metabolites in EMCV infection remain unclear. Kynurenine 3-monooxygenase (KMO) is one of the key regulatory enzymes, which metabolizes kynurenine to 3-hydroxykynurenine in the KP. Therefore, we examined the role of KMO in acute viral infection by comparing between KMO(-/-) mice and KMO(+/+) mice...
November 23, 2016: Immunology Letters
https://www.readbyqxmd.com/read/27888616/ccl2-egf-positive-feedback-loop-between-cancer-cells-and-macrophages-promotes-cell-migration-and-invasion-in-head-and-neck-squamous-cell-carcinoma
#16
Lu Gao, Feng-Qin Wang, Hui-Min Li, Jie-Gang Yang, Jian-Gang Ren, Ke-Fei He, Bing Liu, Wei Zhang, Yi-Fang Zhao
Head and neck squamous cell carcinoma (HNSCC) represents the most frequent malignancy in the head and neck region, and the survival rate has not been improved significantly over the past three decades. It has been reported the infiltrated macrophages contribute to the malignant progression of HNSCC. However, the crosstalk between macrophages and cancer cells remains poorly understood. In the present study, we explored interactions between monocytes/macrophages and HNSCC cells by establishing the direct co-culture system, and found that the crosstalk promoted the migration and invasion of cancer cells by enhancing the invadopodia formation through a CCL2/EGF positive feedback loop...
November 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27888067/allele-and-genotype-frequencies-of-polymorphisms-in-cytokine-genes-in-ethnic-russian-individuals-from-moscow-russia
#17
Alexandra Shadrina, Elena Voronina, Igor Zolotukhin, Maxim Filipenko
Two hundred and twenty eight ethnic Russian individuals from Moscow, Russia, were genotyped at 14 single nucleotide polymorphisms CCL2 A-2578G; VEGFA C-2578A, G-634C, and C+936T; TNF G+419A and G-308A; IL1A G-889A; IL1RN T+1018C; IL6 G-174C and G-572C; IFNG T+874A; IL1B C-511T; IL10 A+1082G; TGFB1 C-509T. Genotypes were determined using real-time polymerase chain reaction with TaqMan probes and polymerase chain reaction followed by melting analysis of dual-labeled probe. Genotype distribution was in accordance with Hardy-Weinberg equilibrium for all studied polymorphisms...
November 22, 2016: Human Immunology
https://www.readbyqxmd.com/read/27883026/inhibition-of-lysophosphatidic-acid-receptors-1-and-3-attenuates-atherosclerosis-development-in-ldl-receptor-deficient-mice
#18
Eva Kritikou, Gijs H M van Puijvelde, Thomas van der Heijden, Peter J van Santbrink, Maarten Swart, Frank H Schaftenaar, Mara J Kröner, Johan Kuiper, Ilze Bot
Lysophosphatidic acid (LPA) is a natural lysophospholipid present at high concentrations within lipid-rich atherosclerotic plaques. Upon local accumulation in the damaged vessels, LPA can act as a potent activator for various types of immune cells through its specific membrane receptors LPA1/3. LPA elicits chemotactic, pro-inflammatory and apoptotic effects that lead to atherosclerotic plaque progression. In this study we aimed to inhibit LPA signaling by means of LPA1/3 antagonism using the small molecule Ki16425...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27878687/aptamers-against-pro-and-anti-inflammatory-cytokines-a-review
#19
REVIEW
Maryam Boshtam, Seddigheh Asgary, Shirin Kouhpayeh, Laleh Shariati, Hossein Khanahmad
Inflammatory disorders result from continuous inflammation in injured sites. Many molecules are involved in this process; the inhibition of which could prevent the inflammation. Chemokines are a group of these biological mediators which are categorized into pro-, anti-, and pro-/anti-inflammatory. Thus, targeting these essential molecules can be an effective way for prevention and control of inflammatory diseases. Various therapeutic agents have been developed for primary and secondary prevention of these disorders, but each of them has its own limitations...
November 23, 2016: Inflammation
https://www.readbyqxmd.com/read/27876507/exercise-induced-cytokine-changes-in-antigen-stimulated-whole-blood-cultures-compared-to-serum
#20
C Pilat, K Krüger, T Frech, F C Mooren
Strenuous exercise is followed by an elevation of many cytokines with inflammation regulating properties. Since most cytokines act at pico- or nanomolar concentrations many investigations failed to detect their concentrations in vivo. Hence, the aim of this study was to evaluate the significance of cytokine measurements (IL-1β, TNF-α, IL-1ra, IL-6, CCL2 and CXCL8) in a stimulated whole-blood culture (sWBC) compared to serum with respect to their exercise-induced kinetics and detection rates. 40 male volunteers (age: 25,5 ± 4,3 years, BMI: 24,00 ± 2,24, VO2peak: 46,9 ± 4,1 ml/kg x min) performed 60 minutes of intensive bicycle exercise (80% VO2peak)...
November 19, 2016: Journal of Immunological Methods
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