Dexamethasone accelerates catabolism of leukotriene C4 in bronchial epithelial cells.
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.
Zaitsu
M
M
Dept of Paediatrics, Faculty of Medicine, Saga Medical School, Saga, Japan. zaitsum@post.saga-med.ac.jp
Hamasaki
Y
Y
Tsuji
K
K
Matsuo
M
M
Fujita
I
I
Aoki
Y
Y
Ishii
E
E
Kohashi
O
O
D000704:Analysis of Variance; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D001980:Bronchi / Q000166:cytology*; D002461:Cell Line, Transformed; D002851:Chromatography, High Pressure Liquid; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D017997:Leukotriene C4 / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D005723:gamma-Glutamyltransferase / Q000096:biosynthesis
D018927:Anti-Asthmatic Agents; D005938:Glucocorticoids; D012333:RNA, Messenger; D017997:Leukotriene C4; D003907:Dexamethasone; D005723:gamma-Glutamyltransferase