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https://www.readbyqxmd.com/read/28233474/induced-pluripotent-stem-cell-derived-endothelial-cells-overexpressing-interleukin-8-receptors-a-b-and-or-c-c-chemokine-receptors-2-5-inhibit-vascular-injury-response
#1
Samantha Giordano, Xiangmin Zhao, Yiu-Fai Chen, Silvio H Litovsky, Fadi G Hage, Tim M Townes, Chiao-Wang Sun, Li-Chen Wu, Suzanne Oparil, Dongqi Xing
Recruitment of neutrophils and monocytes/macrophages to the site of vascular injury is mediated by binding of chemoattractants to interleukin (IL) 8 receptors RA and RB (IL8RA/B) C-C chemokine receptors (CCR) 2 and 5 expressed on neutrophil and monocyte/macrophage membranes. Endothelial cells (ECs) derived from rat-induced pluripotent stem cells (RiPS) were transduced with adenovirus containing cDNA of IL8RA/B and/or CCR2/5. We hypothesized that RiPS-ECs overexpressing IL8RA/B (RiPS-IL8RA/B-ECs), CCR2/5 (RiPS-CCR2/5-ECs), or both receptors (RiPS-IL8RA/B+CCR2/5-ECs) will inhibit inflammatory responses and neointima formation in balloon-injured rat carotid artery...
February 24, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28232185/pcsk9-regulates-the-chemokine-receptor-ccr2-on-monocytes
#2
Jana Grune, Heike Meyborg, Taisiya Bezhaeva, Kai Kappert, Philipp Hillmeister, Ulrich Kintscher, Burkert Pieske, Philipp Stawowy
: Monocyte migration is a key element in atherosclerosis. LDL-C facilitates monocyte migration via induction of CCR2. PCSK9 regulates cell surface expression of the LDL-R and is expressed in vascular smooth muscle cells (VSMCs). The present study was done to investigate the regulation of PCSK9 in VSMCs and its impact on monocyte function. METHODS AND RESULTS: PCSK9 mRNA and protein levels were upregulated in VSMCs by the TLR-4 ligand LPS, whereas TGF-β or angiotensin II had no effect...
February 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28231771/novel-synthetic-analogues-of-avian-%C3%AE-defensin-12-the-role-of-charge-hydrophobicity-and-disulfide-bridges-in-biological-functions
#3
Ming Yang, Chunye Zhang, Michael Z Zhang, Shuping Zhang
BACKGROUND: Avian β-defensins (AvBD) possess broad-spectrum antimicrobial, LPS neutralizing and chemotactic properties. AvBD-12 is a chemoattractant for avian immune cells and mammalian dendritic cells (JAWSII) - a unique feature that is relevant to the applications of AvBDs as chemotherapeutic agents in mammalian hosts. To identify the structural components essential to various biological functions, we have designed and evaluated seven AvBD analogues. RESULTS: In the first group of analogues, the three conserved disulfide bridges were eliminated by replacing cysteines with alanine and serine residues, peptide hydrophobicity and charge were increased by changing negatively charged amino acid residues to hydrophobic (AvBD-12A1) or positively charged residues (AvBD-12A2 and AvBD-12A3)...
February 23, 2017: BMC Microbiology
https://www.readbyqxmd.com/read/28222329/inflammatory-chemokines-and-their-receptors-in-human-visceral-leishmaniasis-gene-expression-profile-in-peripheral-blood-splenic-cellular-sources-and-their-impact-on-trafficking-of-inflammatory-cells
#4
Neetu Singh, Shyam Sundar
Chemokines play an important role in determining cellular composition at inflammatory sites, and as such, influence disease outcome. In this study, we investigated the expression profile and splenic cellular source of various inflammatory chemokines and their receptors in human visceral leishmaniasis (VL). The expression of chemokines or their receptors was measured at the gene and protein level by employing real time qPCR and a cytometric bead array assay, respectively. In addition, the cellular source of chemokines and their receptors in the spleen was identified employing gene expression analyses in sequentially selected cell subsets...
February 18, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28212753/the-trail-induced-cancer-secretome-promotes-a-tumor-supportive-immune-microenvironment-via-ccr2
#5
Torsten Hartwig, Antonella Montinaro, Silvia von Karstedt, Alexandra Sevko, Silvia Surinova, Ankur Chakravarthy, Lucia Taraborrelli, Peter Draber, Elodie Lafont, Frederick Arce Vargas, Mona A El-Bahrawy, Sergio A Quezada, Henning Walczak
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is known for specifically killing cancer cells, whereas in resistant cancers, TRAIL/TRAIL-R can promote metastasis via Rac1 and PI3K. It remains unknown, however, whether and to what extent TRAIL/TRAIL-R signaling in cancer cells can affect the immune microenvironment. Here we show that TRAIL-triggered cytokine secretion from TRAIL-resistant cancer cells is FADD dependent and identify the TRAIL-induced secretome to drive monocyte polarization to myeloid-derived suppressor cells (MDSCs) and M2-like macrophages...
February 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28209525/stromal-vascular-fraction-shows-robust-wound-healing-through-high-chemotactic-and-epithelialization-property
#6
Dong-Sic Chae, Seongho Han, Mina Son, Sung-Whan Kim
BACKGROUND: Although human stromal vascular fraction (SVF) has been regarded as an attractive stem cell source, its therapeutic mechanism in wound healing has not been fully elucidated. AIMS: In this study, we investigated the molecular characteristics and therapeutic property of SVF for wound healing. METHODS: Microarray data showed that SVF cells are enriched with a higher level of wound healing or epithelium development-related genes and micro RNA...
February 13, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28208753/possible-impact-of-190g-a-ccr2-and-%C3%AE-32-ccr5-mutations-on-decrease-of-the-hbv-vaccine-immunogenicity-a-preliminary-report
#7
Maria Ganczak, Karolina Skonieczna-Żydecka, Marzena Drozd-Dąbrowska, Grażyna Adler
Background: Chemokine genetic variations are involved in infectious diseases such as hepatitis B virus (HBV). Several allelic variants might, in theory, affect the outcome of vaccination. Objectives: This study was carried out to examine the associations of Δ32 CCR5 and 190G > A CCR2 polymorphisms with a response to a primary course of three HBV vaccinations. Methods: Between December 2014 and December 2016, patients from three randomly selected primary care clinics in the West Pomeranian region (Poland), 1 month after receiving the third dose of HBV vaccine, were enrolled...
February 8, 2017: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/28202513/myeloid-cells-that-impair-immunotherapy-are-restored-in-melanomas-which-acquire-resistance-to-braf-inhibitors
#8
Shannon M Steinberg, Tamer Shabaneh, Peisheng Zhang, Viktor Martyanov, Zhenghui Li, Brian Malik, Tammara Wood, Andrea Boni, Aleksey Molodtsov, Christina V Angeles, Tyler J Curiel, Michael Whitfield, Mary Jo Turk
Acquired resistance to BRAFV600E inhibitors (BRAFi) in melanoma remains a common clinical obstacle, as is the case for any targeted drug therapy that can be developed given the plastic nature of cancers. While there has been significant focus on the cancer cell-intrinsic properties of BRAFi resistance, the impact of BRAFi resistance on host immunity has not been explored. Here we provide preclinical evidence that resistance to BRAFi in an autochthonous mouse model of melanoma is associated with restoration of myeloid-derived suppressor cells (MDSC) in the tumor microenvironment initially reduced by BRAFi treatment...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28197827/phloretin-prevents-high-fat-diet-induced-obesity-and-improves-metabolic-homeostasis
#9
Sary Alsanea, Mingming Gao, Dexi Liu
Reactive oxygen species generated as a by-product in metabolism play a central role in the development of obesity and obesity-related metabolic complications. The objective of the current study is to explore the possibility to block obesity and improve metabolic homeostasis via phloretin, a natural antioxidant product from apple tree leaves and Manchurian apricot. Both preventive and therapeutic activities of phloretin were assessed using a high-fat diet-induced obesity mouse model. Phloretin was injected intraperitoneally twice weekly into regular and obese mice fed a high-fat diet...
February 14, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28197374/tumor-derived-osteopontin-isoforms-cooperate-with-trp53-and-ccl2-to-promote-lung-metastasis
#10
Ioanna Giopanou, Ioannis Lilis, Vassilios Papaleonidopoulos, Theodora Agalioti, Nikolaos I Kanellakis, Nikolitsa Spiropoulou, Magda Spella, Georgios T Stathopoulos
The lungs are ubiquitous receptacles of metastases originating from various bodily tumors. Although osteopontin (SPP1) has been associated with tumor dissemination, the role of its isoforms in lung-directed metastasis is incompletely understood. We employed syngeneic mouse models of spontaneous and induced lung-targeted metastasis in C57BL/6 mice competent and deficient in both Spp1 alleles. Tumor-derived osteopontin expression was modulated using either stable anti-Spp1 RNA interference, or forced overexpression of intracellular and secreted Spp1 isoforms...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28188247/neurodegeneration-enhances-the-development-of-arthritis
#11
Stefanie C Lang, Ulrike Harre, Pavitra Purohit, Katharina Dietel, Deborah Kienhöfer, Jonas Hahn, Wolfgang Baum, Martin Herrmann, Georg Schett, Dirk Mielenz
The prevalence of neurodegenerative disease and arthritis increases with age. Despite both processes being associated with immune activation and inflammation, little is known about the mechanistic interactions between neurodegenerative disease and arthritis. In this article, we show that tau-transgenic (tau-tg) mice that develop neurodegenerative disease characterized by deposition of tau tangles in the brain are highly susceptible to developing arthritis. Already at steady-state conditions, tau-tg mice exhibit peripheral immune activation that is manifested by higher numbers of granulocytes, plasmablasts, and inflammatory Ly6C(hi) CCR2(+) monocytes, as well as increased levels of proinflammatory cytokines, such as TNF-α and IL-17...
February 10, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28182087/pretreatment-with-fish-oil-based-lipid-emulsion-modulates-muscle-leukocyte-chemotaxis-in-murine-model-of-sublethal-lower-limb-ischemia
#12
Yao-Ming Shih, Juey-Ming Shih, Yu-Chen Hou, Chiu-Li Yeh, Cheng-Che Li, Sung-Ling Yeh
This study investigated the effects of a fish oil- (FO-) based lipid emulsion on muscle leukocyte chemotaxis and inflammatory responses in a murine model of limb ischemia-reperfusion (IR) injury. Mice were assigned randomly to 1 sham (sham) group, 2 ischemic groups, and 2 IR groups. The sham group did not undergo the ischemic procedure. The mice assigned to the ischemic or IR groups were pretreated intraperitoneally with either saline or FO-based lipid emulsion for 3 consecutive days. The IR procedure was induced by applying a 4...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28171673/ccr2-regulates-inflammatory-cell-accumulation-in-the-lung-and-tissue-injury-following-ozone-exposure
#13
Mary Francis, Angela M Groves, Richard Sun, Jessica A Cervelli, Hyejeong Choi, Jeffrey D Laskin, Debra L Laskin
No abstract text is available yet for this article.
November 11, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28168553/ccr2-contributes-to-the-recruitment-of-monocytes-and-leads-to-kidney-inflammation-and-fibrosis-development
#14
Tarcio Teodoro Braga, Matheus Correa-Costa, Reinaldo Correia Silva, Mario Costa Cruz, Meire Ioshie Hiyane, Joao Santana da Silva, Katia Regina Perez, Iolanda Midea Cuccovia, Niels Olsen Saraiva Camara
Chemokines are a large family of proteins that, once associated to its receptor on leukocytes, stimulate their movement and migration from blood to tissues. Once in the tissue, immune cells trigger inflammation that, when uncontrolled, leads to fibrosis development. Among the immune cells, macrophages take a special role in fibrosis formation, since macrophage depletion reflects less collagen deposition. The majority of tissue macrophages is derived from monocytes, especially monocytes expressing the chemokine receptor CCR2...
February 6, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28165741/structural-analysis-of-chemokine-receptor-ligand-interactions
#15
Marta Arimont, Shanliang Sun, Rob Leurs, Martine Smit, Iwan J P De Esch, Chris de Graaf
This review focuses on the construction and application of structural chemokine receptor models for the elucidation of molecular determinants of chemokine receptor modulation and the structure-based discovery and design of chemokine receptor ligands. A comparative analysis of ligand binding pockets in chemokine receptors is presented, including a detailed description of the CXCR4, CCR2, CCR5, CCR9 and US28 X-ray structures, and their implication for modeling molecular interactions of chemokine receptors with small-molecule ligands, peptide ligands, and large antibodies and chemokines...
February 6, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28165470/sodium-chloride-promotes-tissue-inflammation-via-osmotic-stimuli-in-subtotal-nephrectomized-mice
#16
Fumiko Sakata, Yasuhiko Ito, Masashi Mizuno, Akiho Sawai, Yasuhiro Suzuki, Takako Tomita, Mitsuhiro Tawada, Akio Tanaka, Akiyoshi Hirayama, Akihiro Sagara, Takashi Wada, Shoichi Maruyama, Tomoyoshi Soga, Seiichi Matsuo, Enyu Imai, Yoshifumi Takei
Chronic inflammation, which is often associated with high all-cause and cardiovascular mortality, is prevalent in patients with renal failure; however, the precise mechanisms remain unclear. High-salt intake was reported to induce lymphangiogenesis and autoimmune diseases via osmotic stimuli with accumulation of sodium or chloride. In addition, sodium was recently reported to be stored in the extremities of dialysis patients. We studied the effects and mechanisms of high salt loading on tissue and systemic inflammation in subtotal-nephrectomized mice (5/6Nx) and in cultured cells...
February 6, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28161077/m1-macrophages-are-predominantly-recruited-to-the-major-pelvic-ganglion-of-the-rat-following-cavernous-nerve-injury
#17
Hotaka Matsui, Nikolai A Sopko, Johanna L Hannan, Allison A Reinhardt, Max Kates, Takahiro Yoshida, Xiaopu Liu, Fabio Castiglione, Petter Hedlund, Emmanuel Weyne, Maarten Albersen, Trinity J Bivalacqua
INTRODUCTION: Neurogenic erectile dysfunction is a common sequela of radical prostatectomy. The etiology involves injury to the autonomic cavernous nerves, which arise from the major pelvic ganglion (MPG), and subsequent neuroinflammation, which leads to recruitment of macrophages to the injury site. Currently, two macrophage phenotypes are known: neurotoxic M1 macrophages and neuroprotective M2 macrophages. AIM: To examine whether bilateral cavernous nerve injury (BCNI) in a rat model of erectile dysfunction would increase recruitment of neurotoxic M1 macrophages to the MPG...
February 2017: Journal of Sexual Medicine
https://www.readbyqxmd.com/read/28155899/fingolimod-alters-the-transcriptome-profile-of-circulating-cd4-cells-in-multiple-sclerosis
#18
Jörg Friess, Michael Hecker, Luisa Roch, Dirk Koczan, Brit Fitzner, Ines Charlotte Angerer, Ina Schröder, Kristin Flechtner, Hans-Jürgen Thiesen, Alexander Winkelmann, Uwe Klaus Zettl
Multiple sclerosis is a demyelinating disease affecting the central nervous system. T cells are known to contribute to this immune-mediated condition. Fingolimod modulates sphingosine-1-phosphate receptors, thereby preventing the egress of lymphocytes, especially CCR7-expressing CD8+ and CD4+ T cells, from lymphoid tissues. Using Affymetrix Human Transcriptome Arrays (HTA 2.0), we performed a transcriptome profiling analysis of CD4+ cells obtained from the peripheral blood of patients with highly active relapsing-remitting multiple sclerosis...
February 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28150777/pathologically-expanded-peripheral-t-helper-cell-subset-drives-b-cells-in-rheumatoid-arthritis
#19
Deepak A Rao, Michael F Gurish, Jennifer L Marshall, Kamil Slowikowski, Chamith Y Fonseka, Yanyan Liu, Laura T Donlin, Lauren A Henderson, Kevin Wei, Fumitaka Mizoguchi, Nikola C Teslovich, Michael E Weinblatt, Elena M Massarotti, Jonathan S Coblyn, Simon M Helfgott, Yvonne C Lee, Derrick J Todd, Vivian P Bykerk, Susan M Goodman, Alessandra B Pernis, Lionel B Ivashkiv, Elizabeth W Karlson, Peter A Nigrovic, Andrew Filer, Christopher D Buckley, James A Lederer, Soumya Raychaudhuri, Michael B Brenner
CD4(+) T cells are central mediators of autoimmune pathology; however, defining their key effector functions in specific autoimmune diseases remains challenging. Pathogenic CD4(+) T cells within affected tissues may be identified by expression of markers of recent activation. Here we use mass cytometry to analyse activated T cells in joint tissue from patients with rheumatoid arthritis, a chronic immune-mediated arthritis that affects up to 1% of the population. This approach revealed a markedly expanded population of PD-1(hi)CXCR5(-)CD4(+) T cells in synovium of patients with rheumatoid arthritis...
1, 2017: Nature
https://www.readbyqxmd.com/read/28148720/distinct-functions-of-cxcr4-ccr2-and-cx3cr1-direct-dendritic-cell-precursors-from-the-bone-marrow-to-the-lung
#20
Hideki Nakano, Miranda R Lyons-Cohen, Gregory S Whitehead, Keiko Nakano, Donald N Cook
Precursors of dendritic cells (pre-DCs) arise in the bone marrow (BM), egress to the blood, and finally migrate to peripheral tissue, where they differentiate to conventional dendritic cells (cDCs). Upon their activation, antigen-bearing cDCs migrate from peripheral tissue to regional lymph nodes (LNs) in a manner dependent on the chemokine receptor, CCR7. To maintain immune homeostasis, these departing cDCs must be replenished by new cDCs that develop from pre-DCs, but the molecular signals that direct pre-DC trafficking from the BM to the blood and peripheral tissues remain poorly understood...
February 1, 2017: Journal of Leukocyte Biology
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