Involvement of gaseous low molecular monoxides in the cutaneous reverse passive Arthus reaction: cytoprotective action of carbon monoxide

Involvement of gaseous low molecular monoxides in the cutaneous reverse passive Arthus reaction: cytoprotective action of carbon monoxide
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DOI:
10.1111/j.1365-2249.2008.03688.x
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发表时间:
2008-08-01
影响因子:
4.6
通讯作者:
Sato, S.
Sato, S.
中科院分区:
医学3区
文献类型:
--
作者:
Shimizu, K.;Bae, S. J.;Sato, S.

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免疫复合物 (IC) 的沉积会引起急性炎症反应并造成组织损伤,有人认为一氧化氮 (NO) 和一氧化碳 (CO) 参与其中。 NO 由 NO 合酶 (NOS) 诱导,CO 由血红素加氧酶 (HO) 产生。 HO同工酶中,HO-1是诱导型。为了评估NO和CO在致病过程中的作用,使用NOS抑制剂、HO-1刺激剂和HO-1抑制剂检查皮肤逆转被动Arthus反应。为了评估反应,我们考虑了水肿、肿瘤坏死因子-α、白介素-6 和中性粒细胞数量。与阳性对照小鼠相比,用HO-1刺激剂处理的小鼠这四个参数的值显着降低。在用 HO-1 抑制剂治疗的小鼠中观察到恰恰相反。这些结果表明 HO-1/CO 信号通路是人类 IC 介导的疾病的治疗靶点。
The deposition of immune complexes (IC) induces an acute inflammatory response with tissue injury, for which the involvement of nitric oxide (NO) and carbon monoxide (CO) has been suggested. NO is induced by NO synthase (NOS) and CO is generated by haeme oxygenase (HO). Among HO isoenzymes, HO-1 is an induced type. To assess the role of NO and CO in the pathogenic process, the cutaneous reverse passive Arthus reaction was examined using NOS inhibitor, HO-1 stimulator and HO-1 inhibitor. To evaluate the reaction we considered oedema, tumour necrosis factor-alpha, interleukin-6, and neutrophil number. The values of these four parameters were significantly reduced in mice treated with HO-1 stimulator as compared with the positive control mice. Quite the reverse was observed in mice treated with HO-1 inhibitor. These results suggest that the HO-1/CO signalling pathway is a therapeutic target for human IC-mediated disease.