Up-regulation of heme oxygenase-1 expression through the Rac1/NADPH oxidase/ROS/p38 signaling cascade mediates the anti-inflammatory effect of 15-deoxy-Δ12,14-prostaglandin J2 in murine macrophages
Up-regulation of heme oxygenase-1 expression through the Rac1/NADPH oxidase/ROS/p38 signaling cascade mediates the anti-inflammatory effect of 15-deoxy-Δ12,14-prostaglandin J2 in murine macrophages
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DOI：
10.1016/j.febslet.2008.02.012
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发表时间：
2008-03-19
期刊：
影响因子：
3.5
通讯作者：
Kim, Byung-Chul
中科院分区：
文献类型：
--
作者：
Hong, Hye-Young;Jeon, Woo-Kwang;Kim, Byung-Chul
我们研究了导致小鼠巨噬细胞响应 15-脱氧-Delta(12,14)-前列腺素 J(2) (15dPGJ(2)) 表达血红素加氧酶-1 (HO-1) 的信号通路。 15dPGJ(2) 引起 Rac1 的剂量和时间依赖性激活，随后通过 NADPH 氧化酶导致活性氧 (ROS) 短暂增加，从而导致下游 p38 激酶激活。 15dPGJ(2)依赖性HO-1表达的抑制显着减弱15dPGJ(2)对LPS诱导的iNOS表达和随后的一氧化氮(NO)产生的抑制。我们的研究结果强烈表明，在体外炎症模型中，15dPGJ(2) 通过 Rac1-NADPH 氧化酶-ROS-p38 信号转导上调 HO-1 发挥其抗炎活性。 (C) 2008 年欧洲生化学会联合会。由 Elsevier B.V. 出版。保留所有权利。
We investigated the signaling pathway that leads to the expression of heme oxygenase-1 (HO-1) in murine macrophages in response to 15-deoxy-Delta(12,14)-prostagiandin J(2) (15dPGJ(2)). 15dPGJ(2) caused dose- and time-dependent activation of Rac1, followed by a transient increase in reactive oxygen species (ROS) via NADPH oxidase, which leads to downstream activation of p38 kinase. Inhibition of 15dPGJ(2)-dependent HO-1 expression significantly attenuated suppression by 15dPGJ(2) Of LPS-induced iNOS expression and subsequent production of nitric oxide (NO). Our findings strongly suggest that 15dPGJ(2) exerts its anti-inflammatory activity through the Rac1-NADPH oxidase-ROS-p38 signaling to the up-regulation of HO-1 in an in vitro inflammation model. (C) 2008 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.