Glucocorticoids decrease c-fosexpression in human nasal polyps in vivo
- aDivision of Rheumatology, Immunology and Allergy, Lower Level, Gorman Building, Georgetown University, 3800 Reservoir Road NW, Washington, DC 20007–2197, USA, bDepartment of Otolaryngology, Georgetown University, 3800 Reservoir Road, Washington, DC 20007–2197, USA
- Dr J N Baraniuk.
- Received 15 January 1998
- Revision requested 27 February 1998
- Revised 16 March 1998
- Accepted 31 March 1998
Abstract
BACKGROUND Activatedc-fos binds tojun proteins to form the activation protein 1 (AP-1) transcription factor that regulates cytokine and other proinflammatory genes.c-Fos may play a key role in nasal polyp formation. Glucocorticoids may exert their anti-inflammatory effects through an interaction of glucocorticoid receptors withAP-1 that leads to mutual inactivation of both factors, and a “default” termination ofAP-1 mediated gene activation. This may explain the beneficial effects of glucocorticoids in the treatment of nasal polyps.
METHODS To test this hypothesis in humans in vivo the immunohistochemical expression ofc-fos-immunoreactive material (c-fos-irm) was assessed in nasal polyps from eight steroid naive subjects, polyps from eight subjects treated with topical beclomethasone dipropionate (BDP), and normal inferior turbinate nasal mucosa (n = 6).
RESULTS mRNA forc-fos was detected in all nasal polyps and normal mucosa. In contrast, c-fos-irm was present in all steroid naive subjects but in only two of the eight subjects treated with BDP (p = 0.007, two-tailed Fisher’s exact test).c-Fos-irm was expressed solely in epithelial cells and glandular structures; it was expressed in normal epithelium and glands, but the staining intensity was low.
CONCLUSION Glucocorticoids appear to modulate expression of c-fos-irm and possibly AP-1 in human airway epithelial cells in vivo.
