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  • Open Access

    ARTICLE

    Synthetic chemokines directly labeled with a fluorescent dye as tools for studying chemokine and chemokine receptor interactions

    Andrew E. Strong1, Anne-Christine Thierry2, Pascal Cousin3, Corinne Moulon4, Stéphane Demotz5

    European Cytokine Network, Vol.17, No.1, pp. 49-59, 2006

    Abstract Chemokines constitute a protein family that exhibit a variety of biological activities involved in normal and pathological physiological processes. CCL11 (eotaxin), CCL19 (MIP-3b), CCL22 (MDC), CXCL11 (I-TAC) and CXCL12 (SDF-1a) chemokines, modified with the Alexa Fluor® 647 fluorescent dye at specific positions along their sequence, were produced by a chemical route and their biological activities were characterized. In a migration assay, fluorescent chemokines were as biologically active as the unmodified forms. All labeled chemokines specifically stained cell lines transfected with the appropriate human chemokine receptors. The specificity of binding was further established by showing that the… More >

  • Open Access

    ARTICLE

    The role of CXCR2 activity in the contact hypersensitivity response in mice

    Franca Cattani1, Anatolia Gallese1, Marco Mosca1, Pasquale Buanne1, Leda Biordi2, Sandro Francavilla3, Gino Coletti4, Luigi Pellegrini1, Gabriella Melillo1, Riccardo Bertini1,*

    European Cytokine Network, Vol.17, No.1, pp. 42-48, 2006

    Abstract The recruitment of polymorphonuclear neutrophil leukocytes (PMN) into a challenge site, and their subsequent activation, are thought to play a role in the elicitation of the contact hypersensitivity (CHS) response. The present study investigated the role played by CXCR2 activity in tissue PMN infiltration and subsequent triggering of CHS. Our results show that the cutaneous infiltration by PMN, induced by hapten challenge was dramatically inhibited in sensitized, CXCR2-deficient (CXCR2-/-) mice. Inhibition of PMN recruitment into the hapten-challenged ears of CXCR2-/- mice was associated with a consistent reduction of the CHS response (ear swelling) in CXCR2-/- mice as… More >

  • Open Access

    ARTICLE

    Development of a systemically-active dual CXCR1/CXCR2 allosteric inhibitor and its efficacy in a model of transient cerebral ischemia in the rat

    Angela Garau1, Riccardo Bertini2, Marco Mosca2, Cinzia Bizzarri2, Roberto Anacardio2, Sara Triulzi1, Marcello Allegretti2, Pietro Ghezzi1, Pia Villa1,3

    European Cytokine Network, Vol.17, No.1, pp. 35-41, 2006

    Abstract The chemokine receptors CXCR1 and CXCR2 present on polymorphonuclear neutrophils (PMN), bind the chemokine CXC ligand 8 (CXCL8)/interleukin-8 (IL-8), and have a key role in PMN recruitment in inflammation. Based on the structure of reparixin, a small-molecular-weight allosteric inhibitor of CXCR1, we designed a dual inhibitor of CXCR1 and CXCR2 with a longer in vivo half-life, DF2156A. This molecule inhibited human and rat PMN migration in response to CXCR1 and CXCR2 ligands and showed an elimination half-life following i.v. administration, of 19 hours. In a rat model of cerebral ischemia/reperfusion induced by temporary (90 min) More >

  • Open Access

    ARTICLE

    Toll-like receptor 4 Asp299Gly/Thr399Ile polymorphisms are a risk factor for Candida bloodstream infection

    Chantal A. A. Van der Graaf1,2, Mihai G. Netea1,2, Servaas A. Morré3, Martin Den Heijer4, Paul E. Verweij2,5, Jos W. M. Van der Meer1,2, Bart Jan Kullberg1,2

    European Cytokine Network, Vol.17, No.1, pp. 29-34, 2006

    Abstract Toll-like receptor (TLR)-4 is an important pattern recognition receptor for Candida albicans, playing a role in innate host defense. We investigated whether there is an association between the TLR4 Asp299Gly or TLR4 Thr399Ile polymorphism, and the occurrence of Candida bloodstream infection. We performed a case-control study, involving 43 patients with a Candida bloodstream infection and 166 healthy individuals. TLR4 Asp299Gly and Thr399Ile polymorphisms were assessed, as well as cytokine production after stimulation of peripheral blood mononuclear cells (PBMC) with Candida albicans. We observed that the prevalence of TLR4 Asp299Gly polymorphism was found to be higher in patients with CandidaMore >

  • Open Access

    ARTICLE

    Neutrophils process interleukin-1β and interleukin-18 precursors in a caspase-1-like fashion – processing is inhibited by human vascular smooth muscle cells

    Elena Westphal1,*, Mona Herzberg2,*, Ingo Neumann1,**, Li Beibei1, Claudia Pilowski1, Chen Li1, Karl Werdan1, Harald Loppnow1,2

    European Cytokine Network, Vol.17, No.1, pp. 19-28, 2006

    Abstract Inflammation contributes to the pathogenesis of atherosclerosis. Proinflammatory cytokines, including interleukin-1 (IL-1), may be involved in the local inflammation occurring in the vessel wall. Vascular smooth muscle cells express the unprocessed IL-1β precursor molecule. Invading leukocytes, such as monocytes or polymorphonuclear granulocytes (PMN) may activate the IL-1β precursor during atherogenesis. Thus, we investigated the capacity of PMN to process IL-1β and IL-18 precursors. Processing was analyzed using Western blot and bioassay for IL-1-activity was performed. As few as 80 to 400 PMN/mL detectably processed preIL-1β. PMN also cleaved the caspase-1 substrate preIL-18. The preIL-1β and… More >

  • Open Access

    ARTICLE

    In vivo electrotransfer of interleukin-10 cDNA prevents endothelial upregulation of activated NF-κB and adhesion molecules following an atherogenic diet

    Stéphane Potteaux1, Virginie Deleuze2, Régine Merval1, Michel F. Bureau2,3, Bruno Esposito1, Daniel Scherman2,3, Alain Tedgui1, Ziad Mallat1

    European Cytokine Network, Vol.17, No.1, pp. 13-18, 2006

    Abstract Objectives. Interleukin (IL)-10 has anti-atherogenic properties. However, the molecular mechanisms involved in IL-10 protection against atherosclerosis in vivo remain poorly understood. In this study, we examined the effect of IL-10 cDNA in vivo electrotransfer on diet-induced, endothelial activation. Methods. C57BL/6J mice were fed an atherogenic diet for 10 days. Expression of VCAM-1 and ICAM-1 was examined in the aortic sinus, a region predisposed to atherogenesis in mice, using immunohistochemistry. NF-κB activation was examined using a monoclonal antibody that selectively reacts with the activated form of the p65 subunit. Results. We detected a low basal expression More >

  • Open Access

    ARTICLE

    Recent advances in the relationship between obesity, inflammation, and insulin resistance

    Jean-Philippe Bastard1, Mustapha Maachi1, Claire Lagathu1, Min Ji Kim1, Martine Caron1, Hubert Vidal2, Jacqueline Capeau1, Bruno Feve3

    European Cytokine Network, Vol.17, No.1, pp. 4-12, 2006

    Abstract It now appears that, in most obese patients, obesity is associated with a low-grade inflammation of white adipose tissue (WAT) resulting from chronic activation of the innate immune system and which can subsequently lead to insulin resistance, impaired glucose tolerance and even diabetes. WAT is the physiological site of energy storage as lipids. In addition, it has been more recently recognized as an active participant in numerous physiological and pathophysiological processes. In obesity, WAT is characterized by an increased production and secretion of a wide range of inflammatory molecules including TNF-α and interleukin-6 (IL-6), which… More >

  • Open Access

    NOTICE OF REDUNDANT PUBLICATION

    Notice of redundant publication

    Didier Fradelizi, Jacques Bertoglio, Vincent Praloran, Mireille Viguier

    European Cytokine Network, Vol.17, No.2, pp. 143-143, 2006

    Abstract This article has no abstract. More >

  • Open Access

    ARTICLE

    White coat hypertension and haemostatic/fibrinolytic balance disorders

    Thomas Makris, Georgios Stavroulakis, Demetrios Papadopoulos, Ioannis Paizis, Panagiota Krespi, Caterina Tsoukala, Antonios Hatzizacharias, Vasilios Votteas

    European Cytokine Network, Vol.17, No.2, pp. 137-141, 2006

    Abstract White coat hypertension (WCH) or isolated clinic hypertension is generally accepted to be a benign condition, although some reports have suggested that it may be associated with an increased cardiovascular event rate or other cardiovascular alterations. It has been previously shown that essential hypertension (EH) is associated with abnormalities in haemostatic/fibrinolytic balance and endothelial function. The aim of our study was to assess the impact of WCH on fibrinolytic balance and endothelial function by measuring plasma levels of plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator antigen (tPA), fibrinogen, and thrombomodulin. These markers were determined in More >

  • Open Access

    ARTICLE

    Association of the IL6-174(G/C) polymorphism with C-reactive protein concentration after weight loss in obese men

    Carita Eklund1, Arja Nenonen2,3,4, Katriina Kukkonen-Harjula3, Patrik Borg3, Mikael Fogelholm3,5, Seppo Laine6, Heini Huhtala7, Terho Lehtimäki4, Mikko Hurme1,8

    European Cytokine Network, Vol.17, No.2, pp. 131-135, 2006

    Abstract Elevated plasma concentration of C-reactive protein has emerged as an important predictor of future cardiovascular diseases and metabolic abnormalities in apparently healthy individuals. Obese individuals tend to have elevated C-reactive protein concentrations. Weight loss induces a change in this protein, and single nucleotide polymorphisms in regulating genes might affect this change, since C-reactive protein concentration is known to be approximately 40-50% heritable. Our aim was to study the association between the IL6 -174(G/C), IL1B +3954(C/T) and CRP +1059(G/C) single nucleotide polymorphisms, and CRP concentrations in obese men during a weight reduction program. We genotyped 72… More >

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