The anti-inflammatory effects of soluble epoxide hydrolase inhibitors are independent of leukocyte recruitment.
The anti-inflammatory effects of soluble epoxide hydrolase inhibitors are independent of leukocyte recruitment.
复制标题
DOI：
10.1016/j.bbrc.2011.06.008
复制
发表时间：
2011-07-08
影响因子：
3.1
通讯作者：
Pinkerton, Kent E.
中科院分区：
文献类型：
--
作者：
Davis, Benjamin B.;Liu, Jun-Yan;Tancredi, Daniel J.;Wang, Lei;Simon, Scott I.;Hammock, Bruce D.;Pinkerton, Kent E.
关键词：
过量的白细胞募集到肺部在包括慢性阻塞性肺病在内的几种肺部炎症性疾病的发展或恶化中发挥着核心作用。环氧二十碳三烯酸（Epoxyeicosatrienoic Acids，EAE）是花生四烯酸的细胞色素P-450代谢产物，具有多种生物学功能，包括通过减少粘附分子表达阻断白细胞向炎症内皮细胞的募集。据报道，抑制EET调节酶可溶性环氧化物水解酶（sEH）也具有体内抗炎作用，包括减少白细胞向肺的募集。我们测试了这样的假设，即sEH抑制剂的体内抗炎作用通过与暴露于烟草烟雾后的急性炎症大鼠模型中的雌二醇的体外抗炎作用相同的机制起作用。与先前发表的数据相反，我们发现sEH抑制并没有减少烟草烟雾诱导的白细胞向肺的募集。此外，sEH抑制并没有减少烟草烟雾诱导的粘附分子在肺血管系统中的表达。类似地，大于或等于其报告的有效剂量的浓度的Eglutamine不会减少TNFα诱导的粘附分子表达。这些结果表明，sEH抑制剂的抗炎作用是独立的白细胞募集和Ehrs不减少负责白细胞募集的粘附分子在体外。这表明，sEH抑制通过EET阻止粘附分子表达来阻止白细胞募集的广泛观点是不可重现的。
Excess leukocyte recruitment to the lung plays a central role in the development or exacerbation of several lung inflammatory diseases including and chronic obstructive pulmonary disease. Epoxyeicosatrienoic acids (EETs) are cytochrome P-450 metabolites of arachidonic acid reported to have multiple biological functions, including blocking of leukocyte recruitment to inflamed endothelium in cell culture through reduction of adhesion molecule expression. Inhibition of the EET regulatory enzyme, soluble epoxide hydrolase (sEH) also has been reported to have anti-inflammatory effects in vivo including reduced leukocyte recruitment to the lung. We tested the hypothesis that the in vivo anti-inflammatory effects of sEH inhibitors act through the same mechanisms as the in vitro anti-inflammatory effects of EETs in a rat model of acute inflammation following exposure to tobacco smoke. Contrary to previously published data, we found that sEH inhibition did not reduce tobacco smoke-induced leukocyte recruitment to the lung. Furthermore, sEH inhibition did not reduce tobacco smoke-induced adhesion molecule expression in the lung vasculature. Similarly, concentrations of EETs greater than or equal to their reported effective dose did not reduce TNFα induced expression of the adhesion molecules. These results suggest that the anti-inflammatory effects of sEH inhibitors are independent of leukocyte recruitment and EETs do not reduce the adhesion molecules responsible for leukocyte recruitment in vitro. This demonstrates that the widely held belief that sEH inhibition prevents leukocyte recruitment via EET prevention of adhesion molecule expression is not reproducible.
登录
查看更多内容
影响因子：
5.7
作者：
Liu JY;Park SH;Morisseau C;Hwang SH;Hammock BD;Weiss RH
通讯作者：
Weiss RH
影响因子：
5.8
作者：
Bolton SJ;Pinnion K;Oreffo V;Foster M;Pinkerton KE
通讯作者：
Pinkerton KE
影响因子：
3.2
作者：
Moraes, TJ;Zurawska, JH;Downey, GP
通讯作者：
Downey, GP
影响因子：
3.8
作者：
Moran, JH;Mitchell, LA;Grant, DF
通讯作者：
Grant, DF
影响因子：
8.3
作者：
Imig, JD;Zhao, XY;Hammock, BD
通讯作者：
Hammock, BD