Pterostilbene 4'-β-Glucoside Attenuates LPS-Induced Acute Lung Injury via Induction of Heme Oxygenase-1.
Pterostilbene 4'-β-Glucoside Attenuates LPS-Induced Acute Lung Injury via Induction of Heme Oxygenase-1.
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DOI：
10.1155/2018/2747018
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发表时间：
2018
影响因子：
--
通讯作者：
Chung HT
中科院分区：
文献类型：
--
作者：
Park J;Chen Y;Zheng M;Ryu J;Cho GJ;Surh YJ;Sato D;Hamada H;Ryter SW;Kim UH;Joe Y;Chung HT
血红素加氧酶-1 (HO-1) 可以发挥抗炎和抗氧化作用。急性肺损伤（ALI）与炎症增加以及促炎细胞和介质在空腔和肺实质中的流入有关。在这项研究中，我们证明紫檀芪 4'-β-葡萄糖苷 (4-PG)（抗氧化剂紫檀芪 (PTER) 的糖基化形式）在用作预处理或治疗后处理时，可以预防脂多糖 (LPS-) 或铜绿假单胞菌 (P. aeruginosa-) 诱导的 ALI，通过 HO-1的诱导。为了确定 HO-1 是否介导 4-PG 的抗氧化和抗炎作用，我们将 Hmox-1 基因缺陷的小鼠置于 LPS 诱导的 ALI 中，并评估了支气管肺泡灌洗 (BAL) 液中的组织学变化、HO-1 表达和促炎细胞因子水平。 4-PG 通过改善肺组织病理变化和减少促炎细胞因子，对 LPS 或铜绿假单胞菌诱导的 ALI 表现出保护作用。此外，4-PG 显着增加细胞和小鼠肺组织中 HO-1 的表达。糖基化形式的紫檀芪 (4-PG) 在诱导 HO-1 表达方面比 PTER 更有效。 Hmox-1 的基因缺失消除了 4-PG 对 LPS 诱导的炎症反应的保护作用。此外，我们发现 4-PG 以依赖于 HO-1 的方式降低细胞内 ROS 水平和线粒体 (mt) ROS 产生。 HO-1 反应产物一氧化碳 (CO)（而非胆绿素或铁）的药理学应用为 Hmox-1 缺陷型巨噬细胞提供保护。综上所述，这些结果表明 4-PG 可以增加 HO-1 的表达，这在改善细胞内和线粒体 ROS 产生以及下调 LPS 诱导的炎症反应中发挥着关键作用。因此，这些发现强烈表明 HO-1 介导 4-PG 的抗氧化和抗炎作用。
Heme oxygenase-1 (HO-1) can exert anti-inflammatory and antioxidant effects. Acute lung injury (ALI) is associated with increased inflammation and influx of proinflammatory cells and mediators in the airspaces and lung parenchyma. In this study, we demonstrate that pterostilbene 4′-β-glucoside (4-PG), the glycosylated form of the antioxidant pterostilbene (PTER), can protect against lipopolysaccharide- (LPS-) or Pseudomonas aeruginosa- (P. aeruginosa-) induced ALI when applied as a pretreatment or therapeutic post-treatment, via the induction of HO-1. To determine whether HO-1 mediates the antioxidant and anti-inflammatory effects of 4-PG, we subjected mice genetically deficient in Hmox-1 to LPS-induced ALI and evaluated histological changes, HO-1 expression, and proinflammatory cytokine levels in bronchoalveolar lavage (BAL) fluid. 4-PG exhibited protective effects on LPS- or P. aeruginosa-induced ALI by ameliorating pathological changes in lung tissue and decreasing proinflammatory cytokines. In addition, HO-1 expression was significantly increased by 4-PG in cells and in mouse lung tissues. The glycosylated form of pterostilbene (4-PG) was more effective than PTER in inducing HO-1 expression. Genetic deletion of Hmox-1 abolished the protective effects of 4-PG against LPS-induced inflammatory responses. Furthermore, we found that 4-PG decreased both intracellular ROS levels and mitochondrial (mt) ROS production in a manner dependent on HO-1. Pharmacological application of the HO-1 reaction product carbon monoxide (CO), but not biliverdin or iron, conferred protection in Hmox-1-deficient macrophages. Taken together, these results demonstrate that 4-PG can increase HO-1 expression, which plays a critical role in ameliorating intracellular and mitochondrial ROS production, as well as in downregulating inflammatory responses induced by LPS. Therefore, these findings strongly suggest that HO-1 mediates the antioxidant and anti-inflammatory effects of 4-PG.
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影响因子：
6.1
作者：
Chiou, Yi-Siou;Tsai, Mei-Ling;Pan, Min-Hsiung
通讯作者：
Pan, Min-Hsiung
影响因子：
4.1
作者：
Emre, Yalin;Hurtaud, Corinne;Cassard-Doulcier, Anne-Marie
通讯作者：
Cassard-Doulcier, Anne-Marie
DOI：
10.1016/j.bbagen.2015.09.018
发表时间：
2015-12-01
影响因子：
3
作者：
Cheng, Hui-Teng;Yen, Chung-Jen;Hung, Kuan-Yu
通讯作者：
Hung, Kuan-Yu
影响因子：
3.7
作者：
Bishayee, Anupam;Waghray, Abhijeet;Darvesh, Altaf S.
通讯作者：
Darvesh, Altaf S.
影响因子：
6.4
作者：
CANNON, JG;TOMPKINS, RG;DINARELLO, CA
通讯作者：
DINARELLO, CA