Beneficial effects of heme oxygenase-1 up-regulation in the development of experimental inflammation induced by zymosan
Beneficial effects of heme oxygenase-1 up-regulation in the development of experimental inflammation induced by zymosan
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DOI：
10.1124/jpet.103.057992
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发表时间：
2003-12-01
影响因子：
3.5
通讯作者：
Alcaraz, J
中科院分区：
文献类型：
--
作者：
Vicente, AM;Guillén, MI;Alcaraz, J
血红素氧合酶-1（HO-1）是氧化应激综合反应的一部分。这种酶可能在一些动物模型中发挥抗炎作用，尽管确切的机制尚未完全了解。我们研究了HO-1在酵母多糖诱导的小鼠气囊炎症反应中的作用。酵母多糖给药诱导HO-1蛋白表达的白细胞迁移到渗出液中，最高水平的后期阶段的这种反应（24 - 48小时）。这伴随着铁蛋白诱导和胆红素积累，表明这种酶在我们的模型中是活性的。HO-1的表达酵母多糖治疗部分减少氨基胍，这表明内源性一氧化氮的参与机制，导致HO-1的合成酵母多糖注射小鼠气囊。血红素管理的HO-1的上调导致抑制一氧化氮合酶-2活性，细胞浸润到气囊渗出液，血浆渗出。渗出液中的白三烯B 4水平在该反应的早期阶段（4 h）显著降低，而白细胞介素-1 β和肿瘤坏死因子-α在所有时间点均受到抑制。锌原卟啉IX抑制HO-1活性防止了氯化血红素给药引起的大部分影响。我们的研究结果表明，HO-1发挥抗炎作用的酵母多糖在小鼠气囊的反应，并支持这种酶在炎症过程的调制中的作用。
Heme oxygenase-1 (HO-1) is part of the integrated response to oxidative stress. This enzyme may exert anti-inflammatory effects in some animal models, although the precise mechanisms are not fully understood. We have examined the role of HO-1 in the inflammatory response induced by zymosan in the mouse air pouch. Zymosan administration induced HO-1 protein expression in leukocytes migrating to exudates, with maximal levels in the late phase of this response ( 24 - 48 h). This was accompanied by ferritin induction and bilirubin accumulation, indicating that this enzyme is active in our model. HO-1 expression by zymosan treatment was partly reduced by aminoguanidine, suggesting the participation of endogenous nitric oxide in the mechanisms leading to HO-1 synthesis in the zymosan-injected mouse air pouch. Up-regulation of HO-1 by hemin administration resulted in inhibition of nitric-oxide synthase-2 activity, cellular infiltration into the air pouch exudate, and plasmatic exudation. Leukotriene B 4 levels in exudates were significantly decreased in the early phase of this response ( 4 h), whereas interleukin-1beta and tumor necrosis factor-alpha were inhibited at all time points. Inhibition of HO-1 activity by zinc protoporphyrin IX prevented most of the effects caused by hemin administration. Our results indicate that HO-1 exerts anti-inflammatory effects on the response to zymosan in the mouse air pouch and support a role for this enzyme in the modulation of inflammatory processes.