根皮素通过调控NF-κB和MAPK途径来抑制脂多糖（LPS）诱导的小鼠急性肺损伤
2016/10/09
摘要
根皮素，它可以从苹果树中分离得到，对巨噬细胞有明显的抗炎和抗氧化作用。我们前期报道了根皮素能抑制炎症反应、降低细胞间黏附分子1（ICAM-1）在白细胞介素（IL）- 1β激活人肺上皮细胞中的表达。在本研究中我们评估根皮素是否能改善脂多糖（LPS）诱导的小鼠急性肺损伤。在气管内进行LPS给药诱导肺损伤之前，在腹腔注射根皮素对小鼠连续7天给药。随后的分析表明，根皮素能显著抑制LPS诱导的肺组织中性粒细胞浸润、降低IL-6的水平、降低血清和支气管肺泡灌洗液中肿瘤坏死因子（TNF）-α的水平。我们还发现，根皮素能调控髓过氧化物酶活性和超氧化物歧化酶活性，降低炎症肺组织中的趋化因子、促炎细胞因子和ICAM-1的基因表达水平。根皮素还显著降低核因子-κB的磷酸化（NF-κB）和磷酸腺苷活化蛋白激酶（MAPK），从而限制了炎症反应，同时促进血红素氧合酶（HO）-1和核因子红细胞2相关因子2的表达，这两者都是细胞保护。我们的研究结果表明，机械性地，根皮素通过阻断肺损伤小鼠NF-κB和MAPK信号通路来抑制炎症和氧化应激途径。
关键词：急性肺损伤；细胞因子；脂多糖；核因子-kB；根皮素
（杨冬 审校）
Int Immunopharmacol. 2016 Aug 30;40:98-105. doi: 10.1016/j.intimp.2016.08.035. [Epub ahead of print]
Phloretin attenuates LPS-induced acute lung injury in mice via modulation of the NF-κB and MAPK pathways.
Huang WC1, Lai CL2, Liang YT3, Hung HC3, Liu HC3, Liou CJ4.
Author information
Abstract
Phloretin, which can be isolated from apple trees, has demonstrable anti-inflammatory and anti-oxidant effects in macrophages. We previously reported that phloretin could inhibit the inflammatory response and reduce intercellular adhesion molecule 1 (ICAM-1) expression in interleukin (IL)-1β-activated human lung epithelial cells. In the present study we now evaluate whether phloretin exposure could ameliorate lipopolysaccharide (LPS)-induced acute lung injury in mice. Intra-peritoneal injections of phloretin were administered to mice for 7 consecutive days, prior to the induction of lung injury by intra-tracheal administration of LPS. Our subsequent analyses demonstrated that phloretin could significantly suppress LPS-induced neutrophil infiltration of lung tissue, and reduce the levels of IL-6 and tumor necrosis factor (TNF)-α in serum and bronchoalveolar lavage fluid. We also found that phloretin modulated myeloperoxidase activity and superoxide dismutase activity, with decreased gene expression levels for chemokines, proinflammatory cytokines, and ICAM-1 in inflamed lung tissue. Phloretin also significantly reduced the phosphorylation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK), thus limiting the inflammatory response, while promoting expression of heme oxygenase (HO)-1 and nuclear factor erythroid 2-related factor 2, both of which are cytoprotective. Our findings suggest that, mechanistically, phloretin attenuates the inflammatory and oxidative stress pathways that accompany lung injury in mice via blockade of the NF-κB and MAPK pathways.
Copyright © 2016. Published by Elsevier B.V.
KEYWORDS:Acute lung injury; Cytokine; Lipopolysaccharide; NF-κB; Phloretin
Int Immunopharmacol. 2016 Aug 30;40:98-105. doi: 10.1016/j.intimp.2016.08.035. [Epub ahead of print]
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