J Asthma Allergy Clin Immunol.  2003 Dec;23(4):810-817.

Effect of GRbeta expression on steroid-induced transcriptional activity in airway epithelial cells

• Jee YK
• Kim YS
• Park JS
• Lee KY

Abstract

BACKGROUND
It has been known that GRbeta(90 kDa), an alternative splicing variant, can not bind ligand and may act as a domiant negative inhibitor of GRalpha. But there is little report on the effect of GRbeta on steroid-induced transrepression, and GRbeta as a dominant negative inhibitor is still uncertain.
OBJECTIVE
The aim of this study is to investigate the functional role of GRbeta expression in steroid-induced transcriptional activity. METHODS: Steroid-induced transactivation was measured by using pGRE luciferase reporter gene in A549 cell line and steroid-induced transrepression was measured by using stable A549 IgGkappa-NFkappaB luciferase cell line, which contained the minimal IL-8 promoter region. Effect of GRbeta expression on steroid-induced transactivation or transrepression were investigated by comparing the results with or without pCMV GRbeta transfection by lipopectamine plus method. TNF-alpha was used as an activator of IL-8 and RU486 was used as a steroid antagonist. RESULTS: GRbeta expression inhibited steroid-induced transactivation, but did not inhibit steroid-induced transrepression. GRbeta expression caused transrepression of IL-8 under the pretreatment of RU486. CONCLUSION: The study suggests that GRbeta may not act as a dominant negative inhibitor of GRalpha, in the steroid-induced transrepression. Furthermore GRbeta looks having a suppressive activity on IL-8 transactivation.

Keyword

glucocorticoid receptor; steroid; transcription

MeSH Terms

Alternative Splicing
Cell Line
Epithelial Cells*
Genes, Reporter
Interleukin-8
Luciferases
Mifepristone
Promoter Regions, Genetic
Receptors, Glucocorticoid
Transcriptional Activation
Transfection
Tumor Necrosis Factor-alpha
Interleukin-8
Luciferases
Mifepristone
Receptors, Glucocorticoid
Tumor Necrosis Factor-alpha