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Am J Physiol Lung Cell Mol Physiol 275: L372-L378, 1998;
1040-0605/98 $5.00
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Vol. 275, Issue 2, L372-L378, August 1998

Glucocorticoid regulation of GM-CSF: evidence for transcriptional mechanisms in airway epithelial cells

Karissa K. Adkins1, Tricia D. Levan1,2, Roger L. Miesfeld3, and John W. Bloom1,2

Departments of 1 Pharmacology and 3 Biochemistry and 2 Respiratory Sciences Center, University of Arizona, Tucson, Arizona 85724

Inflammation plays a central role in the pathogenesis of asthma. Glucocorticoids are first-line anti-inflammatory therapy in the treatment of asthma and are effective inhibitors of inflammatory cytokines. Clinical data demonstrate that granulocyte-macrophage colony-stimulating factor (GM-CSF) production by airway epithelial cells may be an important target of inhaled glucocorticoid therapy. We examined the regulatory mechanisms of GM-CSF expression by interleukin-1beta (IL-1beta ) and the synthetic glucocorticoid dexamethasone in the BEAS-2B human bronchial epithelial cell line. IL-1beta stimulation resulted in a 15-fold induction of GM-CSF protein, which was associated with a corresponding 47-fold maximal induction of GM-CSF mRNA levels. Treatment with the transcriptional inhibitor actinomycin D before IL-1beta stimulation completely abolished induction of GM-CSF mRNA, whereas incubation with cycloheximide had no effect. Taken together, these data demonstrate that IL-1beta induction of GM-CSF is mediated through transcriptional mechanisms. Dexamethasone treatment of BEAS-2B cells produced an 80% inhibition of IL-1beta -induced GM-CSF protein and a 51% inhibition of GM-CSF mRNA. GM-CSF mRNA was rapidly degraded in these cells, and dexamethasone treatment did not significantly affect this decay rate. We conclude that, in the BEAS-2B bronchial epithelial cell line, IL-1beta induction and dexamethasone repression of GM-CSF expression are mediated predominantly through transcriptional mechanisms.

granulocyte-macrophage colony-stimulating factor; asthma; bronchial epithelium; interleukin-1beta ; dexamethasone


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