实验性变应性脑脊髓炎在缺乏12/15-脂氧合酶或5-脂氧合酶的小鼠中会加重。

Experimental allergic encephalomyelitis is exacerbated in mice deficient for 12/15-lipoxygenase or 5-lipoxygenase.

作者信息

Emerson Mitchell R, LeVine Steven M

机构信息

Department of Molecular and Integrative Physiology, Ralph L. Smith Mental Retardation Research Center, University of Kansas Medical Center, Kansas City, KS 66160, USA.

出版信息

Brain Res. 2004 Sep 17;1021(1):140-5. doi: 10.1016/j.brainres.2004.06.045.

DOI:10.1016/j.brainres.2004.06.045

PMID:15328042

Abstract

12/15-Lipoxygenase (12/15-LO) produces 15-hydroxyeicosatetraenoic acid (15-HETE) and 13-hydroxyoctadecadienoic acid (13-HODE) which are agonists for peroxisome proliferator-activated receptor-gamma (PPARgamma). PPARgamma agonists reduce clinical severity of experimental allergic encephalomyelitis (EAE), an animal model of multiple sclerosis. In contrast, 5-lipoxygenase (5-LO) produces the generally proinflammatory leukotrienes (LTs) which would be expected to worsen EAE. We tested the hypotheses that EAE severity would be exacerbated in 12/15-LO-deficient mice and attenuated in 5-LO-deficient mice. 12/15-LO deficiency conferred a significantly worse disease course, and surprisingly, 5-LO deficiency also caused significantly more severe EAE compared to control mice. These data suggest that PPARgamma-regulated gene expression and that 5-LO production of certain LTs have the ability to diminish EAE. Continued analysis will provide insight into the endogenous LO-generated effectors that assist in tempering EAE.

摘要

12/15-脂氧合酶（12/15-LO）产生15-羟基二十碳四烯酸（15-HETE）和13-羟基十八碳二烯酸（13-HODE），它们是过氧化物酶体增殖物激活受体γ（PPARγ）的激动剂。PPARγ激动剂可降低实验性变应性脑脊髓炎（EAE，一种多发性硬化症的动物模型）的临床严重程度。相比之下，5-脂氧合酶（5-LO）产生通常具有促炎作用的白三烯（LTs），预计会加重EAE。我们检验了以下假设：EAE严重程度在12/15-LO缺陷小鼠中会加剧，而在5-LO缺陷小鼠中会减轻。12/15-LO缺陷导致疾病进程明显更糟，令人惊讶的是，与对照小鼠相比，5-LO缺陷也导致EAE明显更严重。这些数据表明PPARγ调节基因表达，并且某些LTs的5-LO产生具有减轻EAE的能力。持续的分析将深入了解有助于缓解EAE的内源性脂氧合酶产生的效应物。