کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2531536 | 1558933 | 2015 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Targeting glycosaminoglycans in the lung by an engineered CXCL8 as a novel therapeutic approach to lung inflammation
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کلمات کلیدی
TNFαSDC4brochoalveolar lavageHMVEC-LSyndecan-4BALMIP-2GM-CSFGAGinflammation - التهاب( توروم) COPD - بیماری مزمن انسدادی ریهChronic obstructive pulmonary disease - بیماری مزمن انسدادی ریهtumor necrosis factor alpha - تومور نکروز عامل آلفاHuman lung microvascular endothelial cells - سلولهای اندوتلیوم میکروویو انسانی ریه انسانTobacco smoke - سیگار کشیدن دودCystic fibrosis - فیبروز کیستیکgranulocyte macrophage colony-stimulating factor - ماکروفاژ گرانولوسیت عامل کلونی تحریک کنندهProtein engineering - مهندسی پروتئینNeutrophils - نوتروفیل هاHeparan sulfate - هپاران سولفاتmacrophage inflammatory protein 2 - پروتئین التهابی ماکروفاژ 2Chemokine - کموکاین یا کموکین Glycosaminoglycan - گلیکوزآمینوگلیکان
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب سلولی و مولکولی
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چکیده انگلیسی
It is broadly recognized that chemokine-activated neutrophils play a crucial role in the inflammation and disruption of lung tissue observed in several acute and chronic lung diseases. Since glycosaminoglycan side chains of proteoglycans act as chemokine co-receptors in inflammation, we have used a CXCL8-based dominant-negative mutant, dnCXCL8, to displace neutrophil-related chemokines in murine lungs using models of lung inflammation. Treatment with dnCXCL8 resulted in a dose-dependent reduction of neutrophil counts in bronchoalveolar lavage (BAL) of mice exposed to lipopolysaccharide after intravenous, subcutaneous and intratracheal administration. A strong and significant therapeutic effect was achieved already at a dose of 40 µg/kg of dnCXCL8. A similar dose response, but showing a broader spectrum of reduced inflammatory cells and soluble inflammatory markers, was observed in a murine model of tobacco smoke (TS)-induced lung inflammation. The broad spectrum of reduced inflammatory cells and markers can be due to the strong inhibition of neutrophil extravasation into the lung parenchyma, and/or to a relatively broad protein displacement profile of dnCXCL8 which may compete not only with wtCXCL8 for glycosaminoglycan-binding but possibly also with other related glycosaminoglycan-binding pro-inflammatory chemokines. Overall our results demonstrate that antagonizing CXCL8/glycosaminoglycan binding reduces lung inflammation as well as associated lung tissue damage due to LPS and TS and may therefore be a new therapeutic approach for lung pathologies characterized by a neutrophilic inflammatory phenotype.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmacology - Volume 748, 5 February 2015, Pages 83-92
Journal: European Journal of Pharmacology - Volume 748, 5 February 2015, Pages 83-92
نویسندگان
Tiziana Adage, Viktoria Konya, Corinna Weber, Elisabeth Strutzmann, Thomas Fuchs, Christina Zankl, Tanja Gerlza, Dalibor Jeremic, Akos Heinemann, Andreas J. Kungl,