Ulinastatin, an elastase inhibitor, inhibits the increased mRNA expression of prostaglandin H2 synthase-type 2 in Kawasaki disease.
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 H2 synthase (PHS)-2, as determined by reverse transcription-polymerase chain reaction, was markedly enhanced, and thromboxane A2 (TXA2)-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.
Zaitsu
M
M
Department of Pediatrics, Saga Medical School, Saga, Japan. g9609@post.saga-med.ac.jp
Hamasaki
Y
Y
Tashiro
K
K
Matsuo
M
M
Ichimaru
T
T
Fujita
I
I
Tasaki
H
H
Miyazaki
S
S
D001241:Aspirin / Q000494:pharmacology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006023:Glycoproteins / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009080:Mucocutaneous Lymph Node Syndrome / Q000188:drug therapy* / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors*; D010741:Phospholipases A / Q000235:genetics; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis*; D013929:Thromboxane B2 / Q000096:biosynthesis; D013930:Thromboxane-A Synthase / Q000235:genetics
D006023:Glycoproteins; D007527:Isoenzymes; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D013929:Thromboxane B2; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A; D010196:Pancreatic Elastase; D013930:Thromboxane-A Synthase; C028665:urinastatin; D001241:Aspirin