Hemin modulates cytokine expressions in macrophage-derived foam cells via heme oxygenase-1 induction
Hemin modulates cytokine expressions in macrophage-derived foam cells via heme oxygenase-1 induction
复制标题
氯高铁血红素通过血红素加氧酶 1 诱导调节巨噬细胞来源的泡沫细胞中的细胞因子表达。
DOI：
10.1254/jphs.fp0060270
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发表时间：
2007-03-01
影响因子：
3.5
通讯作者：
Zhang, Jing
中科院分区：
文献类型：
--
作者：
Ma, Jian-Li;Yang, Peng-Yuan;Zhang, Jing
载脂泡沫细胞被认为是动脉粥样硬化治疗干预的靶点。一些研究提出了改变巨噬细胞中脂质积聚和炎症反应的新方法。发现泡沫细胞形成过程中的抗炎信号将为抗动脉粥样硬化治疗提供新的有效靶点。本研究的目的是观察氧化低密度脂蛋白（ox-LDL）是否能激活人单核细胞系U937细胞中血红素加氧酶（HO）-1的表达水平，从而增加细胞因子的分泌。我们使用氯化血红素（HO-1激活剂）和锌原卟啉IX（ZnPP IX，HO-1抑制剂）来确定HO-1对细胞因子表达的调节作用。结果表明，氯化血红素可以显著降低促炎细胞因子白细胞介素（IL）-1 β和肿瘤坏死因子（TNF）-α的水平，同时以剂量依赖性方式增加U937泡沫细胞中IL-10的产生。ZnPP IX不显著影响泡沫细胞中的细胞因子水平。我们的研究结果提示HO-1是一个重要的抗炎治疗靶点，通过抑制促炎细胞因子和增强抗炎细胞因子来治疗动脉粥样硬化。
Lipid-laden foam cells were considered to be targets for therapeutic intervention in atherosclerosis. Several studies proposed new approaches to alter both lipid accumulation and inflammatory responses in macrophages. Finding anti-inflammatory signals during foam cell formation would provide new valid targets for anti-atherosclerotic treatment. The aim of the present study was to see whether oxidized low-density lipoprotein (ox-LDL) can active heme oxygenase (HO)-1 expression level in a human monocyte line, U937 cells, associated with the increase of cytokine secretion. We used hemin (HO-1 activator) and zinc protoporphyrin IX (ZnPP IX, HO-1 inhibitor) to determine the effect of HO-1 on the regulation of cytokine expressions. The results showed that hemin can significantly decrease pro-inflammatory cytokines interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha levels, while enhancing IL-10 production in a dose-dependent manner in U937 foam cells. ZnPP IX did not significantly affect cytokine levels in foam cells. Our present results suggested that HO-1 is an important anti-inflammatory therapeutic target through inhibiting pro-inflammatory cytokines and enhancing anti-inflammatory cytokines for the management of atherogenesis.