https://scholars.lib.ntu.edu.tw/handle/123456789/502020
標題: | beta-Nitrostyrene derivatives attenuate LPS-mediated acute lung injury via the inhibition of neutrophil-platelet interactions and NET release | 作者: | YAO-WEN CHANG Tseng, Ching-Ping Lee, Chih-Hsun Hwang, Tsong-Long Chen, Yu-Li Su, Mei-Tzu Chong, Kowit-Yu Lan, Ying-Wei Wu, Chin-Chung Chen, Kung-Ju Lu, Fen-Hua Liao, Hsiang-Ruei Hsueh, Chuen Hsieh, Pei-Wen |
關鍵字: | Acute lung injury; Lipopolysaccharide; Neutrophil extracellular trap; Neutrophil-platelet aggregates; β-nitrostyrene derivatives | 公開日期: | 2018 | 卷: | 314 | 期: | 4 | 起(迄)頁: | 1654-1669 | 來源出版物: | American Journal of Physiology-Lung Cellular and Molecular Physiology | 摘要: | Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) are high-mortality and life-threatening diseases that are associated with neutrophil activation and accumulation within lung tissue. Emerging evidence indicates that neutrophil-platelet aggregates (NPAs) at sites of injury increase acute inflammation and contribute to the development of ALI. Although numerous studies have increased our understanding of the pathophysiology of ALI, there is still a lack of innovative and useful treatments that reduce mortality, emphasizing that there is an urgent need for novel treatment strategies. In this study, a new series of small compounds of β-nitrostyrene derivatives (BNSDs) were synthesized, and their anti-inflammatory bioactivities on neutrophils and platelets were evaluated. The new small compound C7 modulates neutrophil function by inhibiting superoxide generation and elastase release. Compound C7 elicits protective effects on LPS-induced paw edema and acute lung injury via the inhibition of neutrophil accumulation, proinflammatory mediator release, platelet aggregation, myeloperoxidase activity, and neutrophil extracellular trap (NET) release. NET formation was identified as the bridge for the critical interactions between neutrophils and platelets by confocal microscopy and flow cytometry. This research provides new insights for elucidating the complicated regulation of neutrophils and platelets in ALI and sheds further light on future drug development strategies for ALI/ARDS and acute inflammatory diseases. ? 2018 American Physiological Society. All rights reserved. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/502020 | ISSN: | 1040-0605 | DOI: | 10.1152/ajplung.00501.2016 | SDG/關鍵字: | 2 chloro 4 (2 nitrovinyl)phenyl benzoate; 2 methoxy 4 (2 nitrobut 1 eny)phenyl benzoate; 2 methoxy 4 (2 nitrobut 1 enyl)phenyl 2 phenylbenzoate; 2 methoxy 4 (2 nitrobut 1 enyl)phenyl benzoate; 2 methoxy 4 (2 nitroprop 1 enyl)phenyl benzoate; 2 methoxy 4 (2 nitrovinyl)phenyl phenylcarbonate; 2 methoxy 4 (2 nitrovinyl)phenylcyclohezane carboxylate; 2 methoxy 4 (2-nitrovinyl)phenyl 2 phenylacetate; antiinfective agent; beta nitrostyrene derivative; dexamethasone; myeloperoxidase; n [2 methoxy 4 (2 nitrovinyl)phenyl] 2 phenylacetamide; phenyl 2 methoxy 4 (2 nitrovinyl)phenyl carbamate; phospholipase inhibitor; protein tyrosine kinase inhibitor; unclassified drug; beta-nitrostyrene; lipopolysaccharide; styrene derivative; acute lung injury; adult respiratory distress syndrome; animal experiment; animal model; animal tissue; Article; bronchoalveolar lavage fluid; confocal microscopy; controlled study; disease association; drug cytotoxicity; drug determination; drug synthesis; dry weight; enzyme activity; extracellular trap; flow cytometry; human; human cell; image analysis; immunohistochemistry; leukocyte activation; lipopolysaccharide-induced acute lung injury; lung homogenate; lung weight; male; mediator release; mortality; mouse; neutrophil; neutrophil chemotaxis; nonhuman; paw edema; priority journal; thrombocyte; thrombocyte aggregation; acute lung injury; animal; C57BL mouse; cell adhesion; cell culture; chemically induced; drug effect; extracellular trap; immunology; lung edema; metabolism; neutrophil; pathology; thrombocyte; Acute Lung Injury; Animals; Blood Platelets; Cell Adhesion; Cells, Cultured; Extracellular Traps; Lipopolysaccharides; Male; Mice; Mice, Inbred C57BL; Neutrophils; Pulmonary Edema; Styrenes |
顯示於: | 電信工程學研究所 |
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