Heme oxygenase-1 mediates the anti-inflammatory effect of interleukin-10 in mice
Heme oxygenase-1 mediates the anti-inflammatory effect of interleukin-10 in mice
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DOI：
10.1038/nm0302-240
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发表时间：
2002-03-01
期刊：
影响因子：
82.9
通讯作者：
Chau, LY
中科院分区：
文献类型：
--
作者：
Lee, TS;Chau, LY
有效的抗炎性白细胞介素-10（IL-10）的作用机制尚不清楚。在这里，我们表明，在小鼠巨噬细胞中，IL-10诱导血红素加氧酶-1（HO-1）的表达，应激诱导蛋白具有潜在的抗炎作用，通过p38丝裂原活化蛋白激酶依赖性途径。抑制HO-1蛋白合成或活性可显著逆转IL-10对脂多糖（LPS）诱导的肿瘤坏死因子-α产生的抑制作用。另外的实验揭示了一氧化碳（HO-1介导的血红素降解的产物之一）参与IL-10的体外抗炎作用。在体内IL-10对HO-1的诱导作用也很明显。IL-10介导的对LPS诱导的感染性休克小鼠的保护作用显着减弱与HO抑制剂，锌原卟啉共治疗。HO-1作为IL-10下游效应子的鉴定为治疗炎性疾病的改进治疗方法提供了新的可能性。
The mechanisms underlying the action of the potent anti-inflammatory interleukin-10 (IL-10) are poorly understood. Here we show that, in murine macrophages, IL-10 induces expression of heme oxygenase-1 (HO-1), a stress-inducible protein with potential anti-inflammatory effect, via a p38 mitogen-activated protein kinase-dependent pathway. Inhibition of HO-1 protein synthesis or activity significantly reversed the inhibitory effect of IL-10 on production of tumor necrosis factor-alpha induced by lipopolysaccharide (LPS). Additional experiments revealed the involvement of carbon monoxide, one of the products of HO-1-mediated heme degradation, in the anti-inflammatory effect of IL-10 in vitro. Induction of HO-1 by IL-10 was also evident in vivo. IL-10-mediated protection against LPS-induced septic shock in mice was significantly attenuated by cotreatment with the HO inhibitor, zinc protoporphyrin. The identification of HO-1 as a downstream effector of IL-10 provides new possibilities for improved therapeutic approaches for treating inflammatory diseases.