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

• Published in: American journal of physiology. Lung cellular and molecular physiology 1998-08, Vol.275 (2), p.372-L378
• Main Authors: Adkins, Karissa K, Levan, Tricia D, Miesfeld, Roger L, Bloom, John W
• Format: Article
• Language: English
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.1998.275.2.l372

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-1 (IL-1 ) and the synthetic glucocorticoid dexamethasone in the BEAS-2B human bronchial epithelial cell line. IL-1 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-1 stimulation completely abolished induction of GM-CSF mRNA, whereas incubation with cycloheximide had no effect. Taken together, these data demonstrate that IL-1 induction of GM-CSF is mediated through transcriptional mechanisms. Dexamethasone treatment of BEAS-2B cells produced an 80% inhibition of IL-1 -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-1 induction and dexamethasone repression of GM-CSF expression are mediated predominantly through transcriptional mechanisms. granulocyte-macrophage colony-stimulating factor; asthma; bronchial epithelium; interleukin-1 ; dexamethasone