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https://www.readbyqxmd.com/read/27914709/podocyte-specific-chemokine-c-c-motif-receptor-2%C3%A2-overexpression-mediates-diabetic-renal-injury-in%C3%A2-mice
#1
Hanning You, Ting Gao, Wesley M Raup-Konsavage, Timothy K Cooper, Sarah K Bronson, W Brian Reeves, Alaa S Awad
Inflammation is a central pathophysiologic mechanism that contributes to diabetes mellitus and diabetic nephropathy. Recently, we showed that macrophages directly contribute to diabetic renal injury and that pharmacological blockade or genetic deficiency of chemokine (C-C motif) receptor 2 (CCR2) confers kidney protection in diabetic nephropathy. However, the direct role of CCR2 in kidney-derived cells such as podocytes in diabetic nephropathy remains unclear. To study this, we developed a transgenic mouse model expressing CCR2 specifically in podocytes (Tg[NPHS2-Ccr2]) on a nephropathy-prone (DBA/2J) and CCR2-deficient (Ccr2(-/-)) background with heterozygous Ccr2(+/-) littermate controls...
November 30, 2016: Kidney International
https://www.readbyqxmd.com/read/27913649/identification-and-function-of-fibrocytes-in-skeletal-muscle-injury-repair-and-muscular-dystrophy
#2
Xingyu Wang, Wanming Zhao, Richard M Ransohoff, Lan Zhou
We identified and characterized the function of CD45(+)/collagen I(+) fibrocytes in acutely injured skeletal muscle of wild-type (WT) and Ccr2(-/-) mice, and in quadriceps and diaphragm muscles of mdx(5cv) mice, a mouse model for Duchenne muscular dystrophy. Fibrocytes were not detected in peripheral blood of WT mice after acute muscle injury or mdx(5cv) mice. Fibrocytes were detected in acutely injured muscles and in mdx(5cv) quadriceps and diaphragm muscles. These cells expressed F4/80 and CCR2, and they were mostly Ly6C(lo) They expressed a low level of collagens but a high level of profibrotic growth factors as compared with i...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27909248/regulation-of-chemokine-receptor-ccr2-recycling-by-filamin-a-phosphorylation
#3
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/27908893/tracking-monocyte-recruitment-and-macrophage-accumulation-in-atherosclerotic-plaque-progression-using-a-novel-hcd68gfp-apoe-reporter-mouse
#4
Eileen McNeill, Asif J Iqbal, Daniel Jones, Jyoti Patel, Patricia Coutinho, Lewis Taylor, David R Greaves, Keith M Channon
OBJECTIVE: To create a model of atherosclerosis using green fluorescent protein (GFP)-targeted monocytes/macrophages, allowing analysis of both endogenous GFP(+) and adoptively transferred GFP(+) myeloid cells in arterial inflammation. APPROACH AND RESULTS: hCD68GFP reporter mice were crossed with ApoE(-/-) mice. Expression of GFP was localized to macrophages in atherosclerotic plaques and in angiotensin II-induced aortic aneurysms and correlated with galectin 3 and mCD68 expression. Flow cytometry confirmed GFP(+) expression in CD11b(+)/CD64(+), CD11c(+)/MHC-II(HI), and CD11b(+)/F4/80(+) myeloid cells...
December 1, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27902740/extensive-characterization-and-comparison-of-endothelial-cells-derived-from-dermis-and-adipose-tissue-potential-use-in-tissue-engineering
#5
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/27895119/partial-agonist-and-biased-signaling-properties-of-the-synthetic-enantiomers-j113863-ucb35625-at-chemokine-receptors-ccr2-and-ccr5
#6
Jenny Corbisier, Alexandre Huszagh, Céline Galés, Marc Parmentier, Jean-Yves Springael
Biased agonism at G protein coupled receptors constitutes a promising area of research for the identification of new therapeutic molecules. In this study, we identified two novel biased ligands for the chemokine receptors CCR2 and CCR5 and characterized their functional properties. We showed that J113863 and its enantiomer UCB35625, initially identified as high-affinity antagonists for CCR1 and CCR3, also bind with low affinity to the closely related receptors CCR2 and CCR5. Binding of J113863 and UCB35625 to CCR2 or CCR5 resulted in the full or partial activation of the three Gi proteins and the two Go isoforms...
November 28, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27891521/food-derived-natural-compounds-for-pain-relief-in-neuropathic-pain
#7
REVIEW
Eun Yeong Lim, Yun Tai Kim
Neuropathic pain, defined as pain caused by a lesion or disease of the somatosensory nervous system, is characterized by dysesthesia, hyperalgesia, and allodynia. The number of patients with this type of pain has increased rapidly in recent years. Yet, available neuropathic pain medicines have undesired side effects, such as tolerance and physical dependence, and do not fully alleviate the pain. The mechanisms of neuropathic pain are still not fully understood. Injury causes inflammation and immune responses and changed expression and activity of receptors and ion channels in peripheral nerve terminals...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27878909/role-of-mcp-1-in-pleural-effusion-development-in-a-carrageenan-induced-murine-model-of-pleurisy
#8
Sally M Lansley, Hui Min Cheah, Y C Gary Lee
BACKGROUND AND OBJECTIVE: Exudative pleural effusions affect over 1500 patients per million population each year. The pathobiology of pleural exudate formation remains unclear. Our recent study revealed monocyte chemotactic protein-1 (MCP-1) as a key driver of fibrinolytic-induced exudate effusion while another study found a role for MCP-1 in malignant effusion formation. In the present study, we further evaluated the role of MCP-1 in the development of pleural effusion in a mouse model of acute pleural inflammation...
November 22, 2016: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/27871915/inhibition-of-siglec-1-by-lentivirus-mediated-small-interfering-rna-attenuates-atherogenesis-in-apoe-deficient-mice
#9
Yi-Song Xiong, Ai-Lin Wu, Dong Mu, Juan Yu, Ping Zeng, Yi Sun, Jie Xiong
BACKGROUND: Siglec-1 is highly expressed on circulating monocytes and plaque macrophages in atherosclerotic patients, but the exact role of Siglec-1 in atherosclerosis has not been elucidated. METHODS: Lentiviral vector containing small interfering RNA targeting Siglec-1 (Lv-shSiglec-1) or control vector (Lv-shNC) were injected intravenously into 6-week old Apoe(-/-) mice. Then onset of atherosclerosis was observed. RESULTS: Siglec-1 was highly expressed in aortic plaques and it can be down-regulated by Lv-shSiglec-1 injection...
November 15, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27868108/inflammatory-monocytes-hinder-antiviral-b-cell-responses
#10
Stefano Sammicheli, Mirela Kuka, Pietro Di Lucia, Nereida Jimenez de Oya, Marco De Giovanni, Jessica Fioravanti, Claudia Cristofani, Carmela G Maganuco, Benedict Fallet, Lucia Ganzer, Laura Sironi, Marta Mainetti, Renato Ostuni, Kevin Larimore, Philip D Greenberg, Juan Carlos de la Torre, Luca G Guidotti, Matteo Iannacone
Antibodies are critical for protection against viral infections. However, several viruses, such as lymphocytic choriomeningitis virus (LCMV), avoid the induction of early protective antibody responses by poorly understood mechanisms. Here we analyzed the spatiotemporal dynamics of B cell activation to show that, upon subcutaneous infection, LCMV-specific B cells readily relocate to the interfollicular and T cell areas of the draining lymph node where they extensively interact with CD11b(+)Ly6C(hi) inflammatory monocytes...
October 21, 2016: Science Immunology
https://www.readbyqxmd.com/read/27865203/minocycline-prevents-cerebral-malaria-confers-neuroprotection-and-increases-survivability-of-mice-during-plasmodium-berghei-anka-infection
#11
Thittayil Suresh Apoorv, Phanithi Prakash Babu
Cerebral malaria (CM) is a neurological complication arising due to Plasmodium falciparum or Plasmodium vivax infection. Minocycline, a semi-synthetic tetracycline, has been earlier reported to have a neuroprotective role in several neurodegenerative diseases. In this study, we investigated the effect of minocycline treatment on the survivability of mice during experimental cerebral malaria (ECM). The currently accepted mouse model, C57BL/6 mice infected with Plasmodium berghei ANKA, was used for the study...
November 16, 2016: Cytokine
https://www.readbyqxmd.com/read/27863550/cc-chemokine-ligand-2-and-cxc-chemokine-ligand-8-as-neutrophil-chemoattractant-factors-in-canine-idiopathic-polyarthritis
#12
Kohei Murakami, Shingo Maeda, Tomohiro Yonezawa, Naoaki Matsuki
Canine idiopathic polyarthritis (IPA) is characterized by increased numbers of polymorphonuclear leukocytes (PMNs) in the synovial fluid (SF). In humans, CC chemokine ligand 2 (CCL2) and CXC chemokine ligand 8 (CXCL8) recruit monocytes and neutrophils, respectively, and are involved in various inflammatory disorders. The aim of this study was to assess the roles of these chemokines in driving PMNs infiltration into the joints of dogs with IPA. SF samples were collected from dogs with IPA (n=19) and healthy controls (n=8), and the concentrations of SF CCL2 and CXCL8 were determined by ELISA...
December 2016: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/27863141/uvb-irradiation-causes-sting-dependent-production-of-protective-type-1-interferon-in-the-skin-by-recruited-inflammatory-monocytes
#13
Clayton Sontheimer, Denny Liggitt, Keith B Elkon
Objective Photosensitivity is common in patients with systemic lupus, though the mechanisms linking ultraviolet light to flares is not well understood. Here, we asked whether repetitive UVB exposure could induce Type I interferon (IFN-I) in normal mouse skin, and investigated the roles of inflammatory monocytes and plasmacytoid dendritic cells (PDCs) in IFN-I production and development of UVB-induced inflammation. Methods Mice were irradiated with UVB at 100 mJ/cm(2) for five days and cutaneous manifestations examined by mRNA expression of inflammatory and IFN-I response genes, histology, and flow cytometry...
November 11, 2016: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/27862498/all-trans-retinoic-acid-preconditioning-enhances-proliferation-angiogenesis-and-migration-of-mesenchymal-stem-cell-in-vitro-and-enhances-wound-repair-in-vivo
#14
M Pourjafar, M Saidijam, K Mansouri, H Ghasemibasir, F Karimi Dermani, R Najafi
OBJECTIVES: Stem cell therapy is considered to be a suitable alternative in treatment of a number of diseases. However, there are challenges in their clinical application in cell therapy, such as to reduce survival and loss of transplanted stem cells. It seems that chemical and pharmacological preconditioning enhances their therapeutic efficacy. In this study, we investigated effects of all-trans retinoic acid (ATRA) on survival, angiogenesis and migration of mesenchymal stem cells (MSCs) in vitro and in a wound-healing model...
November 10, 2016: Cell Proliferation
https://www.readbyqxmd.com/read/27862204/a-comparison-of-the-immunological-potency-of-burkholderia-lipopolysaccharides-in-endotoxemic-balb-c-mice
#15
Pei-Tan Hsueh, Chiu-Lin Liu, Hsuan-Han Wang, Wei-Fen Ni, Ya-Lei Chen, Jong-Kang Liu
Lipopolysaccharide is one of the virulence factors of the soil-borne pathogens Burkholderia pseudomallei, B. thailandensis, B. cenocepacia and B. multivorans, which cause septic melioidosis (often in B. pseudomallei infections but rarely in B. thailandensis infections) or cepacia syndromes (commonly in B. cenocepacia infections but rarely in B. multivorans infections). The inflammatory responses in Burkholderia LPS-induced endotoxemia were evaluated in this study. Prior to induction, the conserved structures and functions of each purified LPS were determined using electrophoretic phenotypes, the ratios of 3-hydroxytetradecanoic to 3-hydroxyhexadecanoic acid and endotoxin units...
November 2016: Microbiology and Immunology
https://www.readbyqxmd.com/read/27860312/cytochrome-p450-26a1-modulates-natural-killer-cells-in-mouse-early-pregnancy
#16
Chao-Yang Meng, Zhong-Yin Li, Wen-Ning Fang, Zhi-Hui Song, Dan-Dan Yang, Dan-Dan Li, Ying Yang, Jing-Pian Peng
Cytochrome P450 26A1 (CYP26A1) has a spatiotemporal expression pattern in the uterus, with a significant increase in mRNA and protein levels during peri-implantation. Inhibiting the function or expression of CYP26A1 can cause pregnancy failure, suggesting an important regulatory role of CYP26A1 in the maintenance of pregnancy. However, little is known about the exact mechanism involved. In this study, using a pCR3.1-cyp26a1 plasmid immunization mouse model and a Cyp26a1-MO (Cyp26a1-specific antisense oligos) knockdown mouse model, we report that the number of Dolichos biflorus agglutinin (DBA) lectin-positive uterine natural killer (uNK) cells was reduced in pCR3...
November 17, 2016: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27856455/map3k8-modulates-monocyte-state-and-atherogenesis-in-apoe-mice
#17
Carlos Sanz-Garcia, Ángela Sánchez, Constanza Contreras-Jurado, Carmela Cales, Cristina Barranquero, Marta Muñóz, Ramón Merino, Paula Escudero, Maria-Jesús Sanz, Jesús Osada, Ana Aranda, Susana Alemany
OBJECTIVE: Map3k8 (Cot/Tpl2) activates the MKK1/2-ERK1/2, MAPK pathway downstream from interleukin-1R, tumor necrosis factor-αR, NOD-2R, adiponectinR, and Toll-like receptors. Map3k8 plays a key role in innate and adaptive immunity and influences inflammatory processes by modulating the functions of different cell types. However, its role in atherogenesis remains unknown. In this study, we analyzed the role of this kinase in this pathology. APPROACH AND RESULTS: We show here that Map3k8 deficiency results in smaller numbers of Ly6C(high)CD11c(low) and Ly6C(low)CD11c(high) monocytes in ApoE(-)(/-) mice fed a high-fat diet (HFD)...
November 17, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27856294/role-of-the-c-c-chemokine-receptor-2-in-a-murine-model-of-injury-induced-osteoarthritis
#18
L Longobardi, J D Temple, L Tagliafierro, H Willcockson, A Esposito, N D'Onofrio, E Stein, T Li, T J Myers, H Ozkan, M L Balestrieri, V Ulici, R F Loeser, A Spagnoli
OBJECTIVE: We previously found in our embryonic studies that proper regulation of the chemokine CCL12 through its sole receptor CCR2, is critical for joint and growth plate development. In the present study, we examined the role of CCR2 in injury-induced-osteoarthritis (OA). METHOD: We used a murine model of injury-induced-OA (destabilization of medial meniscus, DMM), and systemically blocked CCR2 using a specific antagonist (RS504393) at different times during disease progression...
November 14, 2016: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/27852031/increasing-the-efficacy-of-radiotherapy-by-modulating-the-ccr2-ccr5-chemokine-axes
#19
Kelli A Connolly, Brian A Belt, Nathania M Figueroa, Aditi Murthy, Ankit Patel, Minsoo Kim, Edith M Lord, David C Linehan, Scott A Gerber
Although radiotherapy (RT) is widely used to control tumor growth across many cancer types, there is a relatively high incidence of RT failure exhibited by tumor recurrence, therefore a clear need exists to achieve improved effectiveness of RT. The RT-elicited immune response largely impacts the efficacy of RT and includes immune cells that kill tumor cells, but also immunosuppressive cells, which dampen anti-tumor immunity. Using murine models in which syngeneic tumor cell lines (Colon38, Glioma261, Line1) are grown intramuscularly and treated with 15 Gy local RT, we assessed the effects of RT on both the systemic and intratumoral immune response...
November 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27843457/ccr2-positive-exosome-released-by-mesenchymal-stem-cells-suppresses-macrophage-functions-and-alleviates-ischemia-reperfusion-induced-renal-injury
#20
Bing Shen, Jun Liu, Fang Zhang, Yong Wang, Yan Qin, Zhihua Zhou, Jianxin Qiu, Yu Fan
Mesenchymal stem cells (MSCs) derived exosomes have been shown to have protective effects on the kidney in ischemia/reperfusion-induced renal injury. However, the key components in the exosomes and their potential mechanisms for the kidney protective effects are not well understood. In our current study, we focused on the abundant proteins in exosomes derived from MSCs (MSC-exo) and found that the C-C motif chemokine receptor-2 (CCR2) was expressed on MSC-exo with a high ability to bind to its ligand CCL2. We also proved that CCR2 high-expressed MSC-exo could reduce the concentration of free CCL2 and suppress its functions to recruit or activate macrophage...
2016: Stem Cells International
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