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ORIGINAL ARTICLE

Leukotriene Synthesis Is Increased by Transcriptional Up-Regulation of 5-Lipoxygenase, Leukotriene A4 Hydrolase, and Leukotriene C4 Synthase in Asthmatic Children

, M.D., , M.D., , M.D., , M.D., , M.D. & , M.D.
Pages 147-154 | Published online: 22 Apr 2003
 

Abstract

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, LTA4 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.

Abbreviations
AIAs=

Aspirin-induced asthma

cDNA=

Complementary DNA

cPLA2=

Cytosolic phospholipase A2

CRP=

C-reactive protein

DEPC=

Diethyl pyrocarbonate

dNTP=

Deoxyribonucleoside triphosphate

5-LO=

Five-lipoxygenase

FLAP=

Five-lipoxygenase activating protein

GM-CSF=

Granulocyte-macrophage colony-stimulating factor

HPLC=

High performance liquid chromatography

IL=

Interleukin

LT=

Leukotriene

LTC4 syn=

Leukotriene C4 synthase

mRNA=

Messenger RNA

PBS=

Phosphate-buffered saline

PMNs=

Polymorphonuclear leukocytes

RIA=

Radioimmunoassay

RT-PCR=

Reverse transcriptase polymerase chain reaction

TGF-beta=

Transforming growth factor-beta

WBC=

White blood cell

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