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Eur Respir J 2003; 22:35-42
Copyright ©ERS Journals Ltd 2003

Dexamethasone accelerates catabolism of leukotriene C4 in bronchial epithelial cells

M. Zaitsu1, Y. Hamasaki1, K. Tsuji1, M. Matsuo1, I. Fujita1, Y. Aoki2, E. Ishii1 and O. Kohashi3

Depts of 1 Paediatrics, 2 Internal Medicine and 3 Microbiology, Faculty of Medicine, Saga Medical School

CORRESPONDENCE: M. Zaitsu, Dept of Paediatrics, Faculty of Medicine, Saga Medical School, 5–1–1 Nabeshima, Saga 849-8501, Japan. Fax: 81 952342064. E-mail: zaitsum@post.saga-med.ac.jp

Keywords: cysteinyl leukotrienes, dexamethasone, {gamma}-glutamyl transpeptidase, {gamma}-glutamyl transpeptidase-related enzyme, human bronchial epithelial cells

Received: January 21, 2002
Accepted February 3, 2003

This study was supported, in part, by a grant from the Ministry of Education, Science, Sports and Culture, Tokyo, Japan.

Leukotriene (LT)C4, a potent chemical mediator in bronchial asthma, is metabolised to the less active LTE4 via LTD4 in two consecutive reactions catalysed by enzymes of the glutamyl transpeptidase and dipeptidase families. The activities of these catabolic enzymes may be influenced by glucocorticosteroids. This study was conducted to examine whether this inactivation of LTC4 is affected by dexamethasone (DEX) in transformed human bronchial epithelial cells and normal human bronchial epithelial cells.

After incubation with DEX for 0–5 days, cells were resuspended in the presence of exogenous LTC4, and conversion of LTC4 to LTE4 was measured using high-performance liquid chromatography. {gamma}-Glutamyl transpeptidase (GGT) and GGT-related enzyme (GGTRE) messenger ribonucleic acid (mRNA) expression were examined using reverse transcriptase-polymerase chain reaction analysis, and GGT activity by enzyme assay.

Conversion to LTE4 was accelerated by DEX pretreatment. GGTRE but not GGT mRNA expression was enhanced after incubation with DEX.

The results indicate that dexamethasone transcriptionally upregulates the activity of {gamma}-glutamyl transpeptidase-related enzyme in human bronchial epithelial cells, which accelerates inactivation of leukotriene C4 via conversion to leukotriene E4. This is a novel mechanism of glucocorticosteroids in human bronchial epithelial cells.






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Copyright © 2003 by the European Respiratory Society.