GLUCOCORTICOIDS DECREASE C-FOS EXPRESSION IN HUMAN NASAL POLYPS IN-VIVO

Background-Activated c-fos binds to jun proteins to form the activatio n protein 1 (AP-1) transcription factor that regulates cytokine and ot her proinflammatory genes. c-Fos may play a key role in nasal polyp fo rmation. Glucocorticoids may exert their anti-inflammatory effects thr ough an interaction of glucocorticoid receptors with AP-1 that leads t o mutual inactivation of both factors, and a ''default'' termination o f AP-1 mediated gene activation. This may explain the beneficial effec ts of glucocorticoids in the treatment of nasal polyps. Methods-To tes t this hypothesis in humans in vivo the immunohistochemical expression of c-fos-immunoreactive material (c-fos-irm) was assessed in nasal po lyps from eight steroid naive subjects, polyps from eight subjects tre ated with topical beclomethasone dipropionate nasal mucosa (n = 6). Re sults-mRNA for c-fos was detected in all nasal polyps and normal mucos a. In contrast, c-fos-irm was present in all steroid naive subjects bu t in only two of the eight subjects treated with BDP (p = 0.007, two-t ailed Fisher's exact test), c-Fos-irm was expressed solely in epitheli al cells and glandular structures; it was expressed in normal epitheli um and glands, but the staining intensity was low. Conclusion-Glucocor ticoids appear to modulate expression of c-fos-irm and possibly AP-1 i n human airway epithelial cells in vivo.