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https://www.readbyqxmd.com/read/28923439/peripheral-blood-monocytes-reveal-an-activated-phenotype-in-pediatric-uveitis
#1
Karoline Walscheid, Lisa Neekamp, Arnd Heiligenhaus, Toni Weinhage, Dirk Holzinger, Carsten Heinz, Maren Kasper, Dirk Foell
OBJECTIVE: To characterize peripheral blood monocytes in uveitis associated with juvenile idiopathic arthritis (JIAU). METHODS: Peripheral blood monocytes from children with JIA (either with (n=18) or without uveitis (n=11)), idiopathic anterior uveitis (IAU; n=12) and healthy controls (n=11) were analyzed by flow cytometry. RESULTS: Percentage of CD14+CD86+ monocytes and CD86 expression on single cell level were significantly higher in all patient groups than in controls, whereas no major differences existed between patient groups...
September 15, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28923083/prevention-of-c5ar1-signaling-delays-microglial-inflammatory-polarization-favors-clearance-pathways-and-suppresses-cognitive-loss
#2
Michael X Hernandez, Shan Jiang, Tracy A Cole, Shu-Hui Chu, Maria I Fonseca, Melody J Fang, Lindsay A Hohsfield, Maria D Torres, Kim N Green, Rick A Wetsel, Ali Mortazavi, Andrea J Tenner
BACKGROUND: Pharmacologic inhibition of C5aR1, a receptor for the complement activation proinflammatory fragment, C5a, suppressed pathology and cognitive deficits in Alzheimer's disease (AD) mouse models. To validate that the effect of the antagonist was specifically via C5aR1 inhibition, mice lacking C5aR1 were generated and compared in behavior and pathology. In addition, since C5aR1 is primarily expressed on cells of the myeloid lineage, and only to a lesser extent on endothelial cells and neurons in brain, gene expression in microglia isolated from adult brain at multiple ages was compared across all genotypes...
September 18, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28922396/biochemical-and-immunological-characterization-of-a-novel-monoclonal-antibody-against-mouse-leukotriene-b4-receptor-1
#3
Fumiyuki Sasaki, Tomoaki Koga, Kazuko Saeki, Toshiaki Okuno, Saiko Kazuno, Tsutomu Fujimura, Yasuyuki Ohkawa, Takehiko Yokomizo
Leukotriene B4 (LTB4) receptor 1 (BLT1) is a G protein-coupled receptor expressed in various leukocyte subsets; however, the precise expression of mouse BLT1 (mBLT1) has not been reported because a mBLT1 monoclonal antibody (mAb) has not been available. In this study, we present the successful establishment of a hybridoma cell line (clone 7A8) that produces a high-affinity mAb for mBLT1 by direct immunization of BLT1-deficient mice with mBLT1-overexpressing cells. The specificity of clone 7A8 was confirmed using mBLT1-overexpressing cells and mouse peripheral blood leukocytes that endogenously express BLT1...
2017: PloS One
https://www.readbyqxmd.com/read/28919783/toll-like-receptors-7-and-8-expression-correlates-with-the-expression-of-immune-biomarkers-and-positively-predicts-the-clinical-outcome-of-patients-with-melanoma
#4
Moucheng Zhang, Zhilong Yan, Junjiang Wang, Xueqing Yao
BACKGROUND: Toll-like receptors (TLRs) play a critical role in cancer, yet the clinical relevance of TLR7/8 expression in melanoma remains unclear. This study aimed to evaluate the prognostic value of TLR7/8 mRNA levels in melanoma and their correlation with immune biomarkers relevant to disease progression. METHODS: Normalized gene expression and corresponding clinical data of patients with skin cutaneous melanoma were obtained from two public databases: the Cancer Genome Atlas and GSE19234...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28914666/the-regulation-and-importance-of-monocyte-chemoattractant-protein-1
#5
Vanessa Bianconi, Amirhossein Sahebkar, Stephen L Atkin, Matteo Pirro
PURPOSE OF REVIEW: Monocyte chemoattractant protein (MCP)-1, a chemokine regulating monocyte chemotaxis and T-lymphocyte differentiation by binding to the CC chemokine receptor 2 (CCR2), plays a crucial role in the pathogenesis of inflammatory diseases, atherosclerosis and cancer. This review summarizes the current knowledge on the regulation and importance of the MCP-1/CCR2 axis, focusing on the therapeutic potential of its inhibition. RECENT FINDINGS: Differential modulation of MCP-1 and CCR2 lead to downstream activation pathways, pathogenetic to differing disease conditions characterized by dysregulated monocyte/macrophage tissue recruitment...
September 13, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28912156/neutrophils-are-critical-for-myelin-removal-in-a-peripheral-nerve-injury-model-of-wallerian-degeneration
#6
Jane A Lindborg, Matthias Mack, Richard E Zigmond
Wallerian degeneration (WD) is considered an essential preparatory stage to the process of axonal regeneration. In the peripheral nervous system, infiltrating monocyte-derived macrophages that utilize the chemokine receptor CCR2 to gain entry to injured tissues from the bloodstream, are purportedly necessary for efficient WD. However, our lab has previously reported that myelin clearance in the injured sciatic nerve proceeds unhindered in the Ccr2(-/-) mouse model. Here, we extensively characterize WD in male Ccr2(-/-) mice and identify a compensatory mechanism of WD that is facilitated primarily by neutrophils...
September 14, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28910354/differential-impact-of-the-dual-ccr2-ccr5-inhibitor-cenicriviroc-on-migration-of-monocyte-and-lymphocyte-subsets-in-acute-liver-injury
#7
Tobias Puengel, Oliver Krenkel, Marlene Kohlhepp, Eric Lefebvre, Tom Luedde, Christian Trautwein, Frank Tacke
A hallmark of acute hepatic injury is the recruitment of neutrophils, monocytes and lymphocytes, including natural killer (NK) or T cells, towards areas of inflammation. The recruitment of leukocytes from their reservoirs bone marrow or spleen into the liver is directed by chemokines such as CCL2 (for monocytes) and CCL5 (for lymphocytes). We herein elucidated the impact of chemokine receptor inhibition by the dual CCR2 and CCR5 inhibitor cenicriviroc (CVC) on the composition of myeloid and lymphoid immune cell populations in acute liver injury...
2017: PloS One
https://www.readbyqxmd.com/read/28906029/il-6-production-by-monocytes-is-associated-with-graft-function-decline-in-patients-with-borderline-changes-suspicious-for-acute-t-cell-mediated-rejection-a-pilot-study
#8
Olivier Désy, Stéphanie Béland, Patrice Vallin, Julie Riopel, Eva Latulippe, Nader Najafian, Anil Chandraker, Mohsen Agharazii, Ibrahim Batal, Sacha A De Serres
Although borderline changes (BL) suspicious for acute T-cell-mediated rejection represents a diagnostic category its clinical relevance is questioned leading to heterogeneous therapeutic management. We hypothesized that measuring IL-6 secretion by peripheral blood mononuclear cells identifies patients with ongoing graft damage. We examined the association between secreted IL-6 and the change in estimated glomerular filtration rate at 6 months after the biopsy (ΔeGFR). We then conducted phenotypic and functional studies on patient and mouse innate immune cells in the blood and the kidney...
September 14, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28900008/targeting-cxcr4-dependent-immunosuppressive-ly6c-low-monocytes-improves-antiangiogenic-therapy-in-colorectal-cancer
#9
Keehoon Jung, Takahiro Heishi, Joao Incio, Yuhui Huang, Elizabeth Y Beech, Matthias Pinter, William W Ho, Kosuke Kawaguchi, Nuh N Rahbari, Euiheon Chung, Jun Ki Kim, Jeffrey W Clark, Christopher G Willett, Seok Hyun Yun, Andrew D Luster, Timothy P Padera, Rakesh K Jain, Dai Fukumura
Antiangiogenic therapy with antibodies against VEGF (bevacizumab) or VEGFR2 (ramucirumab) has been proven efficacious in colorectal cancer (CRC) patients. However, the improvement in overall survival is modest and only in combination with chemotherapy. Thus, there is an urgent need to identify potential underlying mechanisms of resistance specific to antiangiogenic therapy and develop strategies to overcome them. Here we found that anti-VEGFR2 therapy up-regulates both C-X-C chemokine ligand 12 (CXCL12) and C-X-C chemokine receptor 4 (CXCR4) in orthotopic murine CRC models, including SL4 and CT26...
September 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28892735/expression-of-the-chemokine-receptors-ccr1-and-ccr2b-is-up-regulated-in-peripheral-blood-b-cells-upon-ebv-infection-and-in-established-lymphoblastoid-cell-lines
#10
Irina Kholodnyuk, Zanna Rudevica, Ainars Leonciks, Barbro Ehlin-Henriksson, Elena Kashuba
In immunocompetent individuals, EBV establishes in B cells an asymptomatic lifelong latent infection controlled by the immune system. Chemokine receptors regulate immune system function. CCR1 and CCR2 share protein sequence similarity and exert responses to multiple chemokines. The role of these receptors in B cells is largely unknown. We show that the mRNA and functional protein expression of CCR1 and CCR2 is induced in ex vivo B cells upon EBV infection and in established lymphoblastoid cell lines (LCLs)...
September 8, 2017: Virology
https://www.readbyqxmd.com/read/28883822/the-role-of-the-chemokine-system-in-tissue-response-to-prosthetic-by-products-leading-to-periprosthetic-osteolysis-and-aseptic-loosening
#11
REVIEW
Tereza Dyskova, Jiri Gallo, Eva Kriegova
Millions of total joint replacements are performed annually worldwide, and the number is increasing every year. The overall proportion of patients achieving a successful outcome is about 80-90% in a 10-20-years time horizon postoperatively, periprosthetic osteolysis (PPOL) and aseptic loosening (AL) being the most frequent reasons for knee and hip implant failure and reoperations. The chemokine system (chemokine receptors and chemokines) is crucially involved in the inflammatory and osteolytic processes leading to PPOL/AL...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28878153/high-throughput-study-of-the-effects-of-celastrol-on-activated-fibroblast-like-synoviocytes-from-patients-with-rheumatoid-arthritis
#12
Zhengyu Fang, Dongyi He, Bo Yu, Feng Liu, Jianping Zuo, Yuxia Li, Qi Lin, Xiaodong Zhou, Qingwen Wang
Celastrol, a natural triterpene, exhibits potential anti-inflammatory activity in a variety of inflammatory diseases. The present study aimed to investigate its biological effect on activated fibroblast-like synoviocytes (FLSs) from patients with rheumatoid arthritis (RA). The primary FLSs of the synovial tissues were obtained from synovial biopsies of patients with RA. The normal human FLS line (HFLS) was used as a control. After the RA-FLSs and HFLSs were treated with or without celastrol, various approaches, including the WST-1 assay, transwell assay, real-time PCR and ELISA analysis, were performed to estimate proliferation, invasion and expression of pro-inflammatory cytokines of the RA-FLSs...
September 6, 2017: Genes
https://www.readbyqxmd.com/read/28862740/dynamics-of-m1-macrophages-in-oral-mucosal-lesions-during-the-development-of-acute-graft-versus-host-disease-in-rats
#13
Kei Seno, Madoka Yasunaga, Hiroshi Kajiya, Kanako Izaki-Hagio, Hiromitsu Morita, Masahiro Yoneda, Takao Hirofuji, Jun Ohno
The role of macrophage infiltrates in oral mucosal acute graft-versus-host disease (AGVHD) remains unclear, although clinical studies suggest that macrophage infiltration correlates directly with the severity of AGVHD. In this study, we investigated the role of M1 macrophage infiltration in the oral mucosa of rats with AGVHD. Lewis rat spleen cells were injected into (Lewis x Brown Norway) F1 rats to induce systemic GVHD. Tongue samples were evaluated using histology, immunohistochemistry, dual immunofluorescence, real-time reverse transcription-polymerase chain reaction, transwell migration assays, and Stamper-Woodruff binding assays...
September 1, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28860501/in-vivo-immune-interactions-of-multipotent-stromal-cells-underlie-their-long-lasting-pain-relieving-effect
#14
Wei Guo, Satoshi Imai, Jia-Le Yang, Shiping Zou, Mineo Watanabe, Yu-Xia Chu, Zaid Mohammad, Huakun Xu, Kamal D Moudgil, Feng Wei, Ronald Dubner, Ke Ren
Systemic infusion of bone marrow stromal cells (BMSCs), a major type of multipotent stromal cells, produces pain relief (antihyperalgesia) that lasts for months. However, studies have shown that the majority of BMSCs are trapped in the lungs immediately after intravenous infusion and their survival time in the host is inconsistent with their lengthy antihyperalgesia. Here we show that long-lasting antihyperalgesia produced by BMSCs required their chemotactic factors such as CCL4 and CCR2, the integrations with the monocytes/macrophages population, and BMSC-induced monocyte CXCL1...
August 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28851810/mertk-cleavage-on-resident-cardiac-macrophages-compromises-repair-after-myocardial-ischemia-reperfusion-injury
#15
Matthew DeBerge, Xin-Yi Yeap, Shirley Dehn, Shuang Zhang, Lubov S Grigoryeva, Sol Misener, Daniele Procissi, Xin Zhou, Daniel C Lee, William A Muller, Xunrong Luo, Carla Rothlin, Ira Tabas, Edward B Thorp
Rationale: Clinical benefits of reperfusion after myocardial infarction (MI) are offset by maladaptive innate immune cell function and therapeutic interventions are lacking. Objective: We sought to test the significance of phagocytic clearance by resident and recruited phagocytes after myocardial ischemia reperfusion (I/R). Methods and Results: In humans, we discovered that clinical reperfusion after MI led to significant elevation of the soluble form of MerTK (i.e. solMER), a critical biomarker of compromised phagocytosis by innate macrophages...
August 29, 2017: Circulation Research
https://www.readbyqxmd.com/read/28851631/strain-specific-helper-t-cell-profile-in-the-gut-associated-lymphoid-tissue
#16
Suzana Stanisavljević, Neda Đedović, Milica Vujičić, Tamara Saksida, Bojan Jevtić, Boško Milovanović, Miljana Momčilović, Đorđe Miljković, Ivana Stojanović
C57BL/6, BALB/c and NOD mice are among the most frequently used strains in autoimmunity research. NOD mice spontaneously develop type 1 diabetes (T1D) and they are prone to induction of experimental autoimmune encephalomyelitis (EAE). Both diseases can be routinely induced in C57BL/6 mice, but not in BALB/c mice. Also, C57BL/6 mice are generally considered T helper (Th)1-biased and BALB/c Th2-biased mice. Having in mind increasingly appreciated role of gut associated lymphoid tissue (GALT) cells in autoimmunity, especially in relation to gut Th17 and regulatory T (Treg) cells, our aim was to determine if there are differences in proportion of CD4(+) T cell populations in mesenteric lymph nodes and Peyer's patches of these mouse strains...
August 26, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28849547/antihyperalgesic-effects-of-ashwagandha-withania-somnifera-root-extract-in-rat-models-of-postoperative-and-neuropathic-pain
#17
Dong Wook Lim, Jae Goo Kim, Eun Yeong Lim, Yun Tai Kim
The root of Withania somnifera, commonly known as ashwagandha, is a traditional herb in the Indian Ayurvedic system of medicine and is used as a tonic. Here, we investigated whether W. somnifera root extract exhibits analgesic effects in plantar incision (PI) and spared nerve injury (SNI) rat models. Mechanical withdrawal threshold (MWT) was measured by von Frey filaments, and pain-related behavior was determined after operation by ultrasonic vocalization (USV) measurements. Indeed, we examined interferon-γ (IFN-γ) and interleukin-10 (IL-10) levels in the isolated dorsal root ganglia (DRG) following SNI in rats using an ELISA cytokine assay...
August 28, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28844797/phenolic-glycolipid-facilitates-mycobacterial-escape-from-microbicidal-tissue-resident-macrophages
#18
C J Cambier, Seónadh M O'Leary, Mary P O'Sullivan, Joseph Keane, Lalita Ramakrishnan
Mycobacterium tuberculosis (Mtb) enters the host in aerosol droplets deposited in lung alveoli, where the bacteria first encounter lung-resident alveolar macrophages. We studied the earliest mycobacterium-macrophage interactions in the optically transparent zebrafish. First-responding resident macrophages phagocytosed and eradicated infecting mycobacteria, suggesting that to establish a successful infection, mycobacteria must escape out of the initially infected resident macrophage into growth-permissive monocytes...
September 19, 2017: Immunity
https://www.readbyqxmd.com/read/28837800/systemic-monocyte-chemotactic-protein-1-inhibition-modifies-renal-macrophages-and-restores-glomerular-endothelial-glycocalyx-and-barrier-function-in-diabetic-nephropathy
#19
Margien G S Boels, Angela Koudijs, M Cristina Avramut, Wendy M P J Sol, Gangqi Wang, Annemarie M van Oeveren-Rietdijk, Anton Jan van Zonneveld, Hetty C de Boer, Johan van der Vlag, Cees van Kooten, Dirk Eulberg, Bernard M van den Berg, Daphne H T IJpelaar, Ton J Rabelink
Inhibition of monocyte chemotactic protein-1 (MCP)-1 with the Spiegelmer emapticap pegol (NOX-E36) shows long-lasting albuminuria-reducing effects in diabetic nephropathy. MCP-1 regulates inflammatory cell recruitment and differentiation of macrophages. Since the endothelial glycocalyx is also reduced in diabetic nephropathy, we hypothesized that MCP-1 inhibition restores glomerular barrier function through influencing macrophage cathepsin L secretion, thus reducing activation of the glycocalyx degrading enzyme heparanase...
August 21, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28836736/ccl2-recruits-t-cells-into-the-brain-in-a-ccr2-independent-manner
#20
Oriane Cédile, Agnieszka Wlodarczyk, Trevor Owens
CCL2 is a chemokine that can be induced during neuroinflammation to recruit immune cells, but its role in the central nervous system (CNS) is unclear. Our aim was to better understand its role. We induced CCL2 in CNS of naive CCL2-deficient mice using intrathecally administered replication-defective adenovirus and examined cell infiltration by flow cytometry. CCL2 expression induced pronounced and unexpected recruitment of regulatory and IFNγ-producing T cells to CNS from blood, possibly related to defective egress of monocytes from CCL2-deficient bone marrow...
August 24, 2017: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
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