Glucocorticoids decrease c-fos expression in human nasal polyps in vivo.
BACKGROUND
Activated c-fos binds to jun 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 with AP-1 that leads to mutual inactivation of both factors, and a "default" termination of AP-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 of c-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 for c-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.


CONCLUSIONS
Glucocorticoids appear to modulate expression of c-fos-irm and possibly AP-1 in human airway epithelial cells in vivo.
Baraniuk
J N
JN
Division of Rheumatology, Immunology and Allergy, Georgetown University, Washington, DC 20007-2197, USA.
Wong
G
G
Ali
M
M
Sabol
M
M
Troost
T
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001507:Beclomethasone / Q000627:therapeutic use*; D004848:Epithelium / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism; D009298:Nasal Polyps / Q000188:drug therapy* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis
D005938:Glucocorticoids; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D001507:Beclomethasone