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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
Natalia Karolina Kordulewska, Elżbieta Kostyra, Anna Cieślińska, Michał Matysiewicz, Ewa Fiedorowicz, Edyta Sienkiewicz-Szłapka
INTRODUCTION: Fexofenadine (FXF) is a third-generation antihistamine drug and osthole is assumed as a natural antihistamine alternative. This paper compares results of histamine, FXF and osthole impact on HRH-1, COX-2, NF-κB-p50, CCR1 mRNA expression. We also measured mRNA expression of IL-1β and CCL5/RANTES in incubated peripheral blood mononuclear cells (PBMC) to compared how histamine, FXF and osthole had influence on expression level and interacts on product secretion. OBJECTIVE: The purpose was to investigate expression pattern in asthma PBMC...
November 10, 2016: Immunobiology
Jan Klocke, Katharina Kopetschke, Anna-Sophie Grießbach, Valerie Langhans, Jens Y Humrich, Robert Biesen, Duska Dragun, Andreas Radbruch, Gerd-Rüdiger Burmester, Gabriela Riemekasten, Philipp Enghard
Renal infiltration of inflammatory cells contributes to the pathogenesis of lupus nephritis (LN). Current knowledge on the recruitment mechanisms relies mainly on findings in rodent models. Here, we assess various chemokine pathways in human LN by comparing urinary chemokine concentrations (in 25 patients with acute LN and in 78 lupus patients without active LN) with the expression of corresponding chemokine receptors on urinary leukocytes (in ten acute LN patients). Nine urinary chemokines were significantly elevated in LN patients and correlated with renal disease activity and urinary cell counts; however, their concentrations displayed considerable interindividual heterogeneity...
October 18, 2016: European Journal of Immunology
Norikazu Kiguchi, Huiping Ding, Christopher M Peters, Nancy D Kock, Shiroh Kishioka, J Mark Cline, Janice D Wagner, Mei-Chuan Ko
Neuroinflammation is a pathological condition that underlies diabetes and affects sensory processing. Given the high prevalence of pain in diabetic patients and crosstalk between chemokines and opioids, it is pivotal to know whether neuroinflammation-associated mediators are dysregulated in the central nervous system of diabetic primates. Therefore, the aim of this study was to investigate whether mRNA expression levels of glial markers, chemokines, and opioid receptors are altered in the spinal cord and thalamus of naturally occurring type 2 diabetic monkeys (n=7) compared with age-matched non-diabetic monkeys (n=6)...
October 14, 2016: Biochimica et Biophysica Acta
Márcio Sousa Jerônimo, Adria do Prado Barros, Vinícius Elord Zen MoritaI, Erika Oliveira Alves, Nathalia Lobão Barroso de Souza, Rosane Mansan de Almeida, Yanna Karla Medeiros Nóbrega, Florêncio Figueiredo Cavalcanti, Rivadávio Amorin, Maria de Fátima Borin, Anamélia Lorenzetti Bocca
PURPOSE: To evaluate the contribution of L-arginine oral or topical rout of administration in the surgical wound healing process. METHODS: L-arginine was orally or topically administrated to mice after a laparotomy model procedure. The wounds were analyzed to evaluate the granulation tissue by HE analysis, collagen deposition, iNOS and cytokines production by immunochemisyry on wound progress. Mice used in this model were healthy, immunosupressed or diabetic and all of them were treated with different concentration of L-arginine and rout of administration...
September 2016: Acta Cirúrgica Brasileira
Mary Francis, Richard Sun, Jessica A Cervelli, Hyejeong Choi, Mili Mandal, Elena V Abramova, Andrew J Gow, Jeffrey D Laskin, Debra L Laskin
Macrophages and inflammatory mediators have been implicated in ozone toxicity. In these studies, we used splenectomized (SPX) mice to assess the contribution of splenic monocytes to pulmonary inflammation and injury induced by ozone. Cells and tissue were collected 24-72 h after exposure of mice to air or ozone (0.8 ppm, 3 h). Following ozone exposure, increased numbers of pro-inflammatory CD11b(+)Ly6C(Hi) and anti-inflammatory CD11b(+)Ly6C(Lo) monocytes were observed in spleens of control (CTL) mice. CD11b(+)Ly6C(Hi) and MMP-9(+) pro-inflammatory macrophages were also observed in lungs of CTL mice after ozone, along with CD11b(+)Ly6C(Lo) and mannose receptor (MR)(+) anti-inflammatory macrophages...
October 5, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
Jorge Luis Costa Carvalho, Auriléia Aparecida de Brito, Ana Paula Ligeiro de Oliveira, Hugo Caire de Castro Faria Neto, Thiago Martini Pereira, Regiane Albertini de Carvalho, Elen Anatriello, Flávio Aimbire
Recent studies show that low-level laser therapy (LLLT) has an important anti-inflammatory action in acute lung inflammation. The present work explored if laser therapy is able to antagonize eosinophils and allergic inflammation induced by oxidative stress in Balb/c mice. Forty-eight hours after challenge, the leukocyte counting, ROS and nitrite/nitrate level, RANTES, CCL3, CCL8 as well as eotaxins were measured in the bronchoalveolar lavage fluid (BALF) of laser-treated mice or not. Into the lung, some chemokines receptors, the iNOS activity and mRNA expression, and the activities of superoxide dismutase (SOD), catalase, gluthatione, NADPH oxidase activities and thiobarbituric acid reactive species (T-Bars) were measured...
September 20, 2016: Journal of Biophotonics
Simona Nemska, Laurent Monassier, Max Gassmann, Nelly Frossard, Reza Tavakoli
Left-ventricular hypertrophy (LVH), a risk factor for heart failure and death, is characterized by cardiomyocyte hypertrophy, interstitial cell proliferation, and leukocyte infiltration. Chemokines interacting with G protein-coupled chemokine receptors may play a role in LVH development by promoting recruitment of activated leukocytes or modulating left-ventricular remodeling. Using a pressure overload-induced kinetic model of LVH in rats, we examined during 14 days the expression over time of chemokine and chemokine receptor mRNAs in left ventricles from aortic-banded vs sham-operated animals...
2016: PloS One
Takamasa Yamamoto, Kenji Kawada, Yoshiro Itatani, Susumu Inamoto, Ryosuke Okamura, Masayoshi Iwamoto, Ei Miyamoto, Toyofumi F Chen-Yoshikawa, Hideyo Hirai, Suguru Hasegawa, Hiroshi Date, Makoto Mark Taketo, Yoshiharu Sakai
PURPOSE: We have reported loss of SMAD4 promotes expression of CCL15 from colorectal cancer (CRC) to recruit CCR1+ myeloid cells through the CCL15-CCR1 axis, which contributes to invasion and liver metastasis. However, the molecular mechanism of lung metastasis is yet to be elucidated. Our purpose is to determine whether similar mechanism is involved in the lung metastasis of CRC. EXPERIMENTAL DESIGN: In a mouse model, we examined whether SMAD4 could affect the metastatic activity of CRC cells to the lung through the CCL15-CCR1 axis...
August 4, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Hui Zhao, Flora Kalish, Ronald J Wong, David K Stevenson
Infiltrating myeloid cells in pregnant uteri play critical roles in the establishment of the placenta and maintenance of normal pregnancies. Their recruitment and proliferation are primarily mediated by the interactions of cytokines and chemokines secreted locally with their corresponding receptors. Heme oxygenase-1 (HO-1) has various physiologic properties that contribute to placental vascular development, with deficiencies in HO-1 associated with pregnancy disorders. Here, we investigated the effect of HO-1 on myeloid cell infiltration into pregnant uteri using a partial HO-1-deficient (Het, HO-1(+/-)) mouse model...
July 28, 2016: Journal of Leukocyte Biology
S Yavuz, T Akdeniz, V Hancer, M Bicakcigil, M Can, G Yanikkaya-Demirel
Behcet's disease (BD) exhibits more severe disease course and higher mortality among male patients. However, underlying mechanisms of gender differences in clinical manifestations and disease severity are unclear. The aim of this study was to determine whether testosterone (T) has any role on BD pathogenesis. We studied peripheral blood mononuclear cells (PBMC) and neutrophils of BD patients and controls. Functional assay of neutrophils, cytokine measurements of culture supernatants and gene expressions on both cells were analyzed before and after T incubation...
September 2016: Genes and Immunity
Ashley C Mays, Xin Feng, James D Browne, Christopher A Sullivan
AIM: To characterize the chemokine pattern in metastatic salivary adenoid cystic carcinoma (SACC). MATERIALS AND METHODS: Real-time polymerase chain reaction (RT-PCR) was used to compare chemokine and chemokine receptor gene expression in two SACC cell lines: SACC-83 and SACC-LM (lung metastasis). Chemokines and receptor genes were then screened and their expression pattern characterized in human tissue samples of non-recurrent SACC and recurrent SACC with perineural invasion...
August 2016: Anticancer Research
Olivier Herbin, Adam G Regelmann, Bhama Ramkhelawon, Erica G Weinstein, Kathryn J Moore, Konstantina Alexandropoulos
OBJECTIVE: The chronic inflammation associated with atherosclerosis is caused by lipid deposition followed by leukocyte recruitment to the arterial wall. We previously showed that the hematopoietic cell-specific adaptor protein Cas- and Hef1-associated signal transducer hematopoietic isoform (Chat-H)/SHEP1 regulated lymphocyte adhesion and migration. In this study, we analyzed the role of Chat-H in atherosclerosis development. APPROACH AND RESULTS: Using Chat-H-deficient bone marrow transplantation in low-density lipoprotein receptor-deficient mice, we found that Chat-H regulated atherosclerotic plaque formation...
September 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
Frauke S Czepluch, Julia Meier, Claudia Binder, Gerd Hasenfuss, Katrin Schäfer
Activated platelets secrete different chemokines, among others CCL5, thereby triggering inflammatory cell recruitment into the vessel wall. Here, we investigated how CCL5 deficiency influences vascular remodeling processes. Experiments were performed in apolipoprotein E and CCL5 double deficient (ApoE(-/-)×CCL5(-/-)) mice, using ApoE(-/-)×CCL5(+/+) mice as controls. The ferric chloride model was applied to induce thrombosis at the site of carotid artery injury within minutes and the formation of a smooth muscle cell-rich neointima within 3weeks...
August 2016: Thrombosis Research
Toshihiro Nanki
  Chemokines induce migration of inflammatory cells. In the synovial tissue of rheumatoid arthritis (RA), abundant chemokines are expressed, which contribute migration of lymphocytes and monocytes/macrophages, stimulation of synovial cells, and angiogenesis. Blockade of CCL2, CCL3, CCL5, CCR1, CCR9, CXCL2, CXCL5, CXCL13, CXCL16, CXCR3, CXCR4, CXCR7, and CX3CL1 showed improvement of arthritis of animal models. Moreover, CCR1 antagonist and anti-CXCL10 antibody reduced arthritis of patients with RA. Chemokine is a promising target for RA therapy...
2016: Nihon Rinshō Men'eki Gakkai Kaishi, Japanese Journal of Clinical Immunology
A Maiga, S Lemieux, C Pabst, V-P Lavallée, M Bouvier, G Sauvageau, J Hébert
Acute myeloid leukemia (AML) is associated with poor clinical outcome and the development of more effective therapies is urgently needed. G protein-coupled receptors (GPCRs) represent attractive therapeutic targets, accounting for approximately 30% of all targets of marketed drugs. Using next-generation sequencing, we studied the expression of 772 GPCRs in 148 genetically diverse AML specimens, normal blood and bone marrow cell populations as well as cord blood-derived CD34-positive cells. Among these receptors, 30 are overexpressed and 19 are downregulated in AML samples compared with normal CD34-positive cells...
2016: Blood Cancer Journal
Annette K Brenner, Håkon Reikvam, Øystein Bruserud
Acute myeloid leukemia (AML) is an aggressive and heterogeneous bone marrow malignancy, the only curative treatment being intensive chemotherapy eventually in combination with allogeneic stem cell transplantation. Both the AML and their neighboring stromal cells show constitutive chemokine release, but chemokines seem to function as regulators of AML cell proliferation only for a subset of patients. Chemokine targeting is therefore considered not only for immunosuppression in allotransplanted patients but also as a possible antileukemic strategy in combination with intensive chemotherapy or as part of disease-stabilizing treatment at least for the subset of patients with chemokine-responsive AML cells...
2016: Frontiers in Immunology
Farshad Foroughi, Aliakbar Amirzargar, Pedram Ahmadpoor, Farshid Noorbakhsh, Mohsen Nafar, Mir Saeed Yekaninejad, Morteza Hosseinzadeh, Sanaz Keshavarz Shabaz, Mehri Barabadi, Mina Ghorbanpour, Abdolfattah Sarrafnejad
BACKGROUND: Leukocyte infiltration into the graft has pivotal effects on kidney transplantation outcome. The present study sought to determine whether the expression of sequential chemokine receptors on CD4(+) and CD8(+) T cells in human renal allograft can predict clinical episodes. METHODS: Blood samples from 52 consecutive renal transplant patients were evaluated at the time of transplantation and at three times (2, 90 and 180days) after transplantation to analyze the expression of CCR1 and CXCR3 on CD4(+) and CD8(+) T cells by flowcytometry...
September 2016: Transplant Immunology
Jianjian Ji, Jingjing Xu, Shuli Zhao, Fei Liu, Jingjing Qi, Yuxian Song, Jing Ren, Tingting Wang, Huan Dou, Yayi Hou
Although major advancements have made in investigating the aetiology of SLE (systemic lupus erythaematosus), the role of MDSCs (myeloid-derived suppressor cells) in SLE progression remains confused. Recently, some studies have revealed that MDSCs play an important role in lupus mice. However, the proportion and function of MDSCs in lupus mice and SLE patients are still poorly understood. In the present study, we investigated the proportion and function of MDSCs using different stages of MRL/lpr lupus mice and specimens from SLE patients with different activity...
August 1, 2016: Clinical Science (1979-)
Mei Huang, Guangyao Li, Tingting Pan, Ya Cheng, Weihua Ren, Weidong Jia, Jinliang Ma, Geliang Xu
The pathogenesis of hepatocellular carcinoma (HCC) is a multi-step process involving many genes. Consequently, single gene targeting therapy has limited efficacy, making combination therapy targeting multiple genes a necessity. Based on our previous findings, we constructed a single vector mediating simultaneous expression of multiple short hairpin RNAs (shRNAs) against human vascular endothelial growth factor receptor 2 (VEGFR2), chemokine C-C motif receptor 1 (CCR1), and epithelial cell adhesion molecule (EpCAM), three genes closely related to HCC progression that act through separate pathways...
May 21, 2016: Oncotarget
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