Glucocorticoids co-interact with lipoxin A4 via lipoxin A4 receptor (ALX) up-regulation
Glucocorticoids co-interact with lipoxin A4 via lipoxin A4 receptor (ALX) up-regulation
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DOI：
10.1016/j.biopha.2006.06.023
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发表时间：
2007-01-01
影响因子：
7.5
通讯作者：
Endo, Hirahito
中科院分区：
文献类型：
--
作者：
Hashimoto, Atsushi;Murakami, Yousuke;Endo, Hirahito
脂氧素A（4）（LXA（4））是通过脂氧合酶产生的类二十烷酸，其在花生四烯酸的许多代谢产物中具有抗炎作用，这些代谢产物主要是促炎的。众所周知，糖皮质激素也具有强烈的抗炎作用，但诱导5-脂氧合酶，这是合成促炎性白三烯所必需的。为了阐明糖皮质激素和脂氧素A（4）在抗炎作用中的相互作用，我们使用皮肤炎症小鼠模型分析了人中性粒细胞上脂氧素A（4）受体（ALX）的体外表达以及糖皮质激素和LXA（4）的体内抗炎作用。地塞米松（Dex）可上调人中性粒细胞ALX mRNA表达。糖皮质激素受体拮抗剂米非司酮可抑制Dex诱导的ALX上调。LXA（4）和/或Dex可降低人中性粒细胞上的CD 11b表达，并抑制LTB 4诱导的小鼠皮炎。这些结果表明糖皮质激素的抗炎作用至少部分依赖于ALX的上调，脂氧素系统可能是LTB 4的负反馈调节剂。(c)2006年，Elsevier Masson SAS。All rights reserved.
Lipoxin A(4) (LXA(4)) is an eicosanoid which is produced via lipoxygenases and characteristic of its anti-inflammatory effect in many metabolites of arachidonic acid, which are mostly pro-inflammatory. Glucocorticoids are well known also for their strong anti-inflammatory action but induce 5-lipoxygenase, essential to synthesize leukotrienes, which are pro-inflammatory. To elucidate the interaction of glucocorticoids and lipoxin A(4) for anti-inflammation, we analyzed in vitro expression of lipoxin A(4) receptor (ALX) on human neutrophils and the in vivo anti-inflammatory effect of glucocorticoids and LXA(4) using a dermal inflammation mouse model. ALX mRNA was up-regulated by dexamethasone (Dex) in human neutrophils. A glucocorticoid receptor antagonist, mifepristone, suppressed up-regulation of ALX induced by Dex. LXA(4) and/or Dex decreased CD11b expression on human neutrophils and suppressed mouse dermatitis induced by LTB4. These results suggest that anti-inflammatory effects of glucocorticoids depend at least partly on up-regulation of ALX and that the lipoxin system could be a negative feedback regulator for LTB4. (c) 2006 Elsevier Masson SAS. All rights reserved.