Ulinastatin, an elastase inhibitor, inhibits the increased mRNA expression of prostaglandin H2 synthase-type 2 in Kawasaki disease
Ulinastatin, an elastase inhibitor, inhibits the increased mRNA expression of prostaglandin H2 synthase-type 2 in Kawasaki disease
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DOI：
10.1086/315332
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发表时间：
2000-03-01
影响因子：
6.4
通讯作者：
Miyazaki, S
中科院分区：
文献类型：
--
作者：
Zaitsu, M;Hamasaki, Y;Miyazaki, S
川崎病是一种病因不明的炎症性疾病，可引起包括冠状动脉炎在内的全血管炎，疾病早期的多形核细胞增多提示中性粒细胞在疾病发病机制中的作用。在川崎病急性期，通过逆转录聚合酶链反应检测前列腺素H-2合成酶(PHS)-2 mRNA表达明显增强，多形核白细胞（PMNL）血栓素A(2) （TXA(2)）合成活性升高。乌司他丁（一种中性粒细胞弹性酶抑制剂）抑制了PHS-2的上调。利用健康志愿者PMNL体外实验，乌司他丁治疗剂量也能抑制脂多糖诱导的PHS-2 mRNA的增强。因此，乌司他丁通过在mRNA水平上抑制PHS-2的新诱导来抑制花生四烯酮PHS代谢，这是该物质的一种新的药理作用。乌司他丁治疗可能是川崎病的另一种治疗方法。
Kawasaki disease is an inflammatory disease of unknown cause that causes panvasculitis, including coronary arteritis, Polymorphonucleocytosis in the early stage of the illness suggests the implication of neutrophils in the pathogenesis of the disease. In the acute phase of Kawasaki disease, mRNA expression of prostaglandin H-2 synthase (PHS)-2, as determined by reverse transcription-polymerase chain reaction, was markedly enhanced, and thromboxane A(2) (TXA(2))-synthesizing activity was increased in polymorphonuclear leukocytes (PMNL). This up-regulation of PHS-2 was suppressed by ulinastatin (a neutrophil-elastase inhibitor) treatment. Lipopolysaccharide-induced enhancement of PHS-2 mRNA was also inhibited by therapeutic doses of ulinastatin in vitro by use of PMNL from healthy volunteers. Thus, ulinastatin inhibits arachidonate PHS metabolism by inhibiting new induction of PHS-2 at the mRNA level, which is a novel pharmacologic action of this substance. Ulinastatin treatment is possibly an additional therapeutic approach to Kawasaki disease.