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Daniela D'Arcangelo, Francesco Facchiano, Giovanni Nassa, Andrea Stancato, Annalisa Antonini, Stefania Rossi, Cinzia Senatore, Martina Cordella, Claudio Tabolacci, Annamaria Salvati, Roberta Tarallo, Alessandro Weisz, Angelo M Facchiano, Antonio Facchiano
Melanoma is the most aggressive skin-cancer, showing high mortality at advanced stages. Platelet Derived Growth Factor Receptor-alpha (PDGFR-alpha) potently inhibits melanoma- and endothelium-proliferation and its expression is significantly reduced in melanoma-biopsies, suggesting that melanoma progression eliminates cells expressing PDGFR-alpha. In the present study transient overexpression of PDGFR-alpha in endothelial (HUVEC) and melanoma (SKMel-28, A375, Preyer) human-cells shows strong anti-proliferative effects, with profound transcriptome and miRNome deregulation...
October 13, 2016: Oncotarget
Sandeep K Shrivastava, Esther Dalko, Delphine Delcroix-Genete, Fabien Herbert, Pierre-André Cazenave, Sylviane Pied
Astrocytes and microglia are activated during cerebral malaria (CM) and contribute to the production and release of several mediators during neuroinflammatory processes. Whether these changes are the consequence of a direct crosstalk between glial cells and the malarial parasite and how these cells participate in the pathogenesis of CM is not yet clear. We therefore examined the interaction of astrocytes and microglia with Plasmodium berghei ANKA-infected red blood cells using primary cell cultures derived from newborn C57BL/6 mice...
October 3, 2016: Glia
William V Perks, Ravinder K Singh, Gareth W Jones, Jason P Twohig, Anwen S Williams, Ian R Humphreys, Philip R Taylor, Simon A Jones, Eddie C Yern Wang
Death receptor 3 (DR3; TNFRSF25) and its tumor necrosis factor-like ligand TL1A (TNFSF15) control several processes in inflammatory diseases through the expansion of effector T cells and the induction of proinflammatory cytokines from myeloid and innate lymphoid cells. Using wild-type (DR3(+/+)) and DR3-knockout (DR3(-/-)) mice, we show that the DR3/TL1A pathway triggers the release of multiple chemokines after acute peritoneal inflammation initiated by a single application of Staphylococcus epidermidis supernatant, correlating with the infiltration of multiple leukocyte subsets...
September 21, 2016: American Journal of Pathology
Esther Dalko, Delphine Genete, Florent Auger, Claire Dovergne, Claire Lambert, Fabien Herbert, Pierre-André Cazenave, Jacques Roland, Sylviane Pied
Cerebral malaria is the deadliest complication of Plasmodium falciparum infection. Its pathophysiology is associated with a strong pro-inflammatory reaction and the activation of glial cells. Among modulators released during the infection, heme seems to play a controversial role in the pathophysiology of malaria. Herein, we first investigated the phenotype of glial cells during cerebral malaria in C57BL/6 mice infected with P. berghei ANKA. Given the fact that high levels of heme were associated with cerebral malaria, we then investigated its impact on microglial, astrocyte, and T cell responses to further clarify its contribution in the neuropathophysiology...
November 2016: Brain, Behavior, and Immunity
M E Hoonakker, L M Verhagen, L van der Maas, B Metz, J P Uittenbogaard, B van de Waterbeemd, C A C M van Els, W van Eden, C F M Hendriksen, A Sloots, W G H Han
Whole cell Bordetella pertussis (wP) vaccines are still used in many countries to protect against the respiratory disease pertussis. The potency of whole-cell pertussis vaccine lots is determined by an intracerebral challenge test (the Kendrick test). This test is criticized due to lack of immunological relevance of the read-out after an intracerebral challenge with B. pertussis. The alternative in vivo test, which assesses specific antibody levels in serum after wP vaccination, is the Pertussis Serological Potency test (PSPT)...
August 17, 2016: Vaccine
Song Han, David H Gonzalo, Michael Feely, Daniel Delitto, Kevin E Behrns, Mark Beveridge, DongYu Zhang, Ryan Thomas, Jose G Trevino, Thomas D Schmittgen, Steven J Hughes
The pancreatic adenocarcinoma (PDAC) microenvironment is largely comprised of fibrotic tumor associated stroma (TAS) that contributes to the lethal biology of PDAC. microRNA (miRNA) are small non-coding RNAs that regulate gene expression. We hypothesized that interactions between PDAC cells and TAS cells within the microenvironment modulate miRNA expression and thus, tumor biology. We observed that miR-205 and members of the miR-200 family (miR-200a, -200b, -200c, -141 and miR-429) were exclusively expressed in PDAC cells, consistent with an epithelial miRNA signature, while miR-145 and miR-199 family members (miR-199a and -199b) were solely expressed in TAS cells, consistent with a stromal miRNA signature...
July 20, 2016: Oncotarget
Andromeda Liñán-Rico, Fabio Turco, Fernando Ochoa-Cortes, Alan Harzman, Bradley J Needleman, Razvan Arsenescu, Mahmoud Abdel-Rasoul, Paolo Fadda, Iveta Grants, Emmett Whitaker, Rosario Cuomo, Fievos L Christofi
BACKGROUND: Clinical observations or animal studies implicate enteric glial cells in motility disorders, irritable bowel syndrome, inflammatory bowel disease, gastrointestinal (GI) infections, postoperative ileus, and slow transit constipation. Mechanisms underlying glial responses to inflammation in human GI tract are not understood. Our goal was to identify the "reactive human enteric glial cell (rhEGC) phenotype" induced by inflammation, and probe its functional relevance. METHODS: Human enteric glial cells in culture from 15 GI-surgical specimens were used to study gene expression, Ca, and purinergic signaling by Ca/fluo-4 imaging and mechanosensitivity...
August 2016: Inflammatory Bowel Diseases
Tang-You Mao, Rui Shi, Wei-Han Zhao, Yi Guo, Kang-Li Gao, Chen Chen, Tian-Hong Xie, Jun-Xiang Li
Qingchang Wenzhong Decoction (QCWZD) is an effective traditional Chinese medicine prescription. Our previous studies have shown that QCWZD has significant efficacy in patients with mild-to-moderate ulcerative colitis (UC) and in colonic mucosa repair in UC rat models. However, the exact underlying mechanism remains unknown. Thus, this study was conducted to determine QCWZD's efficacy and mechanism in dextran sulphate sodium- (DSS-) induced UC rat models, which were established by 7-day administration of 4.5% DSS solution...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
Maiko Akahane, Mikio Watanabe, Naoya Inoue, Yumi Miyahara, Yuya Arakawa, Yuka Inoue, Yuka Katsumata, Yoh Hidaka, Yoshinori Iwatani
Chemokines induce leukocyte chemotaxis and contribute to chronic inflammation. To clarify the association between functional polymorphisms in genes encoding some chemokines and the pathogenesis of Autoimmune thyroid disease (AITD), we genotyped IL8 -251T/A, Regulated upon Activation, Normal T cell Expressed and presumably Secreted (RANTES) - 403G/A, -28C/G, MIG rs2276886G/A, IP10 -1596C/T, Monocyte Chemoattractant Protein1 (MCP1) - 2518G/A and IL16 -295T/C polymorphisms. We genotyped these polymorphisms using the PCR-RFLP method in 149 Graves' disease (GD) patients, including 59 patients with intractable GD and 53 patients with GD in remission, as well as 131 Hashimoto's disease (HD) patients, including 54 patients with severe HD, 46 patients with mild HD and 99 healthy controls...
August 2016: Autoimmunity
Yu-Tung Li, Tomoyuki Nishikawa, Yasufumi Kaneda
Tumours constitute unique microenvironments where various blood cells and factors are exposed as a result of leaky vasculature. In the present study, we report that thrombin enrichment in B16F10 melanoma led to platelet aggregation, and this property was exploited to administer an anticancer cytokine, interferon-gamma induced protein 10 (IP10), through the formation of a platelet-IP10 complex. When intravenously infused, the complex reached platelet microaggregates in the tumour. The responses induced by the complex were solely immune-mediated, and tumour cytotoxicity was not observed...
2016: Scientific Reports
S Badiou, E Tuaillon, J Viljoen, J B Escudié, J P Cristol, M L Newell, P Van de Perre, D Neveu
A residual mother-to-child transmission of HIV through breastfeeding persists despite prophylaxis. We identified breast milk fatty acids (FA) associated with postnatal HIV transmission through breastfeeding in a case-control study. Cases (n=23) were HIV-infected women with an infant who acquired HIV after 6 weeks of age. Controls (n=23) were matched on infant׳s age at sample collection. Adjusting for maternal antenatal plasma CD4 T cell count, cis-vaccenic acid (18:1n-7) and eicosatrienoic acid (20:3n-3) were associated with HIV transmission in opposite dose-response manner: OR (tertile 3 versus tertile 1): 10...
February 2016: Prostaglandins, Leukotrienes, and Essential Fatty Acids
Duygu Övünç Hacıhamdioğlu, Cengiz Zeybek, Faysal Gök, Aysel Pekel, Uğur Muşabak
OBJECTIVE: Increasing evidence suggests that T helper (Th) cells play a significant role in the pathogenesis of hypertension. The aim of this study was to evaluate the effect of obesity and anti-hypertensive treatment on urinary Th1 chemokines. METHODS: The study groups consisted of three types of patients: hypertensive obese, healthy, and non-hypertensive obese. Pre-treatment and post-treatment samples of the hypertensive obese group and one sample from the other two groups were evaluated for urinary chemokine: regulated on activation, normal T cell expressed and secreted (RANTES), interferon-gamma-inducible protein 10 (IP10), and monokine induced by interferon-gamma (MIG)...
September 2015: Journal of Clinical Research in Pediatric Endocrinology
Eun-Ju Lee, Min Wook So, Seokchan Hong, Yong-Gil Kim, Bin Yoo, Chang-Keun Lee
The present study aimed to assess the functions of interleukin (IL)-33 in fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA). Enzyme-linked immunosorbent assays (ELISAs) were used to quantify interleukin (IL)-33 in plasma obtained from patients with RA and osteoarthritis (OA). To evaluate functions of intracellular IL-33, levels of inflammatory mediators and matric metalloproteinases (MMPs) were measured in RA FLS transfected with IL-33 small- interfering RNA (siRNA) or plasmids, and changes in the expression and regulation of nuclear factor kappaB (NF-κB) were determined using western blotting and reporter gene assays...
January 2016: Cytokine
Raffaele Altara, Yu-Mei Gu, Harry A J Struijker-Boudier, Lutgarde Thijs, Jan A Staessen, W Matthijs Blankesteijn
Detecting left ventricular (LV) dysfunction at an early stage is key in addressing the heart failure epidemic. In proteome profiling experiments in mice subjected either to aortic banding or sham, the circulating CXCR3 ligands monokine induced by interferon-γ (MIG) and interferon-γ inducible protein 10 (IP10) were 5 to 40 fold up-regulated at eight weeks. We assessed the diagnostic value of circulating NT-pro BNP and CXCR3 ligands (MIG, IP10, Interferon-inducible T-cell alpha chemo-attractant [I-TAC]) in patients with hypertension (≥140/90 mm Hg) associated with subclinical (n = 19) or symptomatic (n = 16) diastolic LV dysfunction on echocardiography and healthy controls...
2015: PloS One
Maja-Theresa Dieterlen, Katja John, Hartmuth B Bittner, Meinhard Mende, Attila Tarnok, Friedrich W Mohr, Markus J Barten
BACKGROUND: Pharmacodynamic biomarkers that detect changes of immunological functions have been recognized as a helpful tool to increase the efficacy of immunosuppressive drug therapies. However, physiological changes of immunological biomarkers following transplantation are not investigated. Therefore, we assessed frequently used immunological biomarkers of the circulating blood in the first year following heart transplantation (HTx). METHODS: Activation markers CD25 and CD95, intracellular cytokines IL-2 and IFNγ, chemokines IP10 and MIG, and subsets of dendritic cells as well as antibodies against human leukocyte antigens (HLA) and major histocompatibility complex class I-related chain A (MICA) antigens were analyzed at different time points using flow cytometry and Luminex xMAP technology...
2015: Disease Markers
Nikhil Nitin Kulkarni, Hörður Ingi Gunnarsson, Zhiqian Yi, Steinunn Gudmundsdottir, Olafur E Sigurjonsson, Birgitta Agerberth, Gudmundur H Gudmundsson
Glucocorticoids (GCs) have been extensively used as the mainstream treatment for chronic inflammatory disorders. The persistent use of steroids in the past decades and the association with secondary infections warrants for detailed investigation into their effects on the innate immune system and the therapeutic outcome. In this study, we analyse the effect of GCs on antimicrobial polypeptide (AMP) expression. We hypothesize that GC related side effects, including secondary infections are a result of compromised innate immune responses...
February 2016: Immunobiology
Wei Geng, Chung-Mau Lo, Kevin T P Ng, Chang-Chun Ling, Xiang Qi, Chang-Xian Li, Yuan Zhai, Xiao-Bing Liu, Yuen-Yuen Ma, Kwan Man
Tumor recurrence remains an obstacle after liver surgery, especially in living donor liver transplantation (LDLT) for patients with hepatocellular carcinoma (HCC). The acute-phase liver graft injury might potentially induce poor response to chemotherapy in recurrent HCC after liver transplantation. We here intended to explore the mechanism and to identify a therapeutic target to overcome such chemoresistance. The associations among graft injury, overexpression of IP10 and multidrug resistant genes were investigated in a rat liver transplantation model, and further validated in clinical cohort...
September 29, 2015: Oncotarget
Maria Gariup, Azucena Gonzalez, Luisa Lázaro, Ferran Torres, Carles Serra-Pagès, Astrid Morer
OBJECTIVE: The role of inflammation in psychopathology has received great attention over the past decades. Immune system dysfunction and altered cytokine levels have been reported in most psychiatric disorders in adults. Few data are available regarding children and adolescents (C&A), or regarding the relationship between cytokine levels and psychosocial stress. This study investigates the profile of the most described cytokines in a sample of C&A inpatients affected by an acute psychiatric condition requiring hospitalization, in comparison with healthy subjects, as well as possible associations between psychosocial stressors and psychopathology and/or cytokine concentrations...
December 2015: Psychoneuroendocrinology
Roel Polak, Bob de Rooij, Rob Pieters, Monique L den Boer
Acute lymphoblastic leukemia (ALL) cells reside in the bone marrow microenvironment which nurtures and protects cells from chemotherapeutic drugs. The disruption of cell-cell communication within the leukemic niche may offer an important new therapeutic strategy. Tunneling nanotubes (TNTs) have been described as a novel mode of intercellular communication, but their presence and importance in the leukemic niche are currently unknown. Here, we show for the first time that primary B-cell precursor ALL (BCP-ALL) cells use TNTs to signal to primary mesenchymal stromal cells (MSCs)...
November 19, 2015: Blood
Nicolas Noel, Nathalie Lerolle, Camille Lécuroux, Cécile Goujard, Alain Venet, Asier Saez-Cirion, Veronique Avettand-Fenoël, Laurence Meyer, Faroudy Boufassa, Olivier Lambotte
Some HIV controllers (HICs) experience CD4+T cell count loss and/or lose their ability to control HIV. In this study, we investigated the rate of immunologic and/or virologic progression (ImmP/VirP) and its determinants in the ANRS CO21/CODEX cohort. Immunologic progression was defined as a lasting fall in CD4+T cell count below 350/mm(3) or more than 200/mm(3) with a baseline count below 600/mm(3). Virologic progression was defined as a HIV viral load (VL) above 2000 copies/mL on two consecutive determinations...
2015: PloS One
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