Leukotriene synthesis is increased by transcriptional up-regulation of 5-lipoxygenase, leukotriene A(4) hydrolase, and leukotriene C-4 synthase in asthmatic children

Leukotrienes (LTs) are recognized to be important mediators in asthma. Recent studies revealed that LT synthesis is controlled by the regulation of LT-synthesizing enzymes. We determined the synthesis of LTB4 and LTC4 by specific radioimmunoassay, and the messenger RNA (mRNA) expression of LT-synthesizing enzymes by reverse transcriptase polymerase chain reaction in peripheral polymorphonuclear leukocytes, which were obtained from controls and asthmatic children. The synthesis of LTB4 and LTC4, and the mRNA expression of 5-lipoxygenase, LTA(4) hydrolase, and LTC4 synthase were enhanced in the patients. The mRNA expression of LT-synthesizing enzymes was up-regulated, resulting in increased LT synthesis, which may play an important role in the pathogenesis of childhood asthma.