Mechanism of dexamethasone-mediated interleukin-8 gene suppression in cultured airway epithelial cells. Chang, Mary Mann-Jong, Maya Juarez, Dallas M. Hyde, and Reen Wu. 1Center for Comparative Respiratory Biology and Medicine, 2Department of Internal Medicine, School of Medicine, and 3Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California at Davis, Davis, California 95616
APStracts 7:0239L, 2000.
The effects of dexamethasone, a glucocorticoid analog, on interleukin 8 (IL-8) gene expression were studied in cultures of primary human tracheobronchial epithelial cells and an immortalized human bronchial epithelial cell line, HBE1 cells. Dexamethasone inhibited IL-8 mRNA and protein expression in a concentration- and time-dependent manner. The inhibition did not occur at the transcriptional level since both nuclear run-on activity and IL-8 promoter-reporter gene expression assay revealed no significant effect. Instead, there was a change in IL-8 mRNA stability in dexamethasone-treated cultures. Under actinomycin D treatment, IL-8 mRNA was quite stable in dexamethasone-depleted cultures, while in dexamethasone-pretreated cultures, IL-8 message were rapidly degraded within the first hour, then leveled off. When dexamethasone and actinomycin D were added simultaneously to dexamethasone-depleted cultures, IL-8 mRNA remained rather stable. When cycloheximide was used to inhibit new protein synthesis, dexamethasone-dependent inhibition was not observed. These results suggest that a posttranscriptional mechanism, which requires dexamethasone-dependent new protein synthesis, is involved in the regulation of IL-8 mRNA by dexamethasone in airway epithelial cells. 

Received 30 September 1999; accepted in final form 17 July 2000
APS Manuscript Number L322-9.
Article publication pending Am J Physiol Lung Cell Mol Physiol
ISSN 1080-4757 Copyright 2000 The American Physiological Society.
Published in APStracts on 7 November 2000