Lower sensitivity of nasal polyp fibroblasts to glucocorticoid anti-proliferative effects.
BACKGROUND
Treatment with glucocorticoids (GCs) is the cornerstone of nasal polyp (NP) therapy, but some patients respond poorly to them. Fibroblasts are involved in both inflammation and remodelling of NP. We aimed to evaluate whether NP fibroblasts are less sensitive to GCs' anti-proliferative and anti-inflammatory effects, compared to nasal mucosa (NM) fibroblasts.


METHODS
Fibroblasts were obtained from NP (n = 8) from asthmatic patients undergoing endoscopic surgery and NM (n = 8) from patients undergoing nasal corrective surgery. Fibroblasts were stimulated with DMEM at 0.5% or 5% FBS, or TGF-β (5 ng/ml), with or without dexamethasone (10(-11) to 10(-5)M) for different times. Cell proliferation, collagen mRNA expression and IL-6 and IL-8 release were measured.


RESULTS
After 3-days, dexamethasone dose-dependently inhibited proliferation of NM (p < 0.001) but not that of NP fibroblasts. Dexamethasone (10(-6)M) reduced by 25% the proliferation of NM fibroblasts. Dexamethasone also inhibited proliferation of NM (p < 0.01) but not that of NP fibroblasts at 5-days. TGF-β induced collagen-1α1, -1α2, and -3α1 mRNA levels in both NM and NP fibroblasts (p < 0.05), and dexamethasone did not alter TGF-β-induced collagen mRNA levels in either fibroblast type at 24 h. Dexamethasone dose-dependently decreased (p < 0.05) FBS-induced IL-6 and IL-8 release in both NM and NP fibroblasts at 4 h, although at 10(-8)M, dexamethasone inhibited cytokine production in NM (p < 0.05) but not in NP fibroblasts.


CONCLUSIONS
This impaired sensitivity of nasal polyp fibroblasts to in vitro glucocorticoid effects concurs in part with the poor clinical response that these nasal polyp patients show to glucocorticoid treatment.
Pujols
Laura
L
Clinical and Experimental Respiratory Immunoallergy, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Villarroel 170, 08036 Barcelona, Catalonia, Spain. lpujols@clinic.ub.es
Fuentes-Prado
Mireya
M
Fernández-Bertolín
Laura
L
Alobid
Isam
I
Roca-Ferrer
Jordi
J
Mullol
Joaquim
J
Picado
César
C
D000328:Adult; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000187:drug effects / Q000378:metabolism; D003907:Dexamethasone / Q000627:therapeutic use*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009298:Nasal Polyps / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D005938:Glucocorticoids; D015850:Interleukin-6; D016209:Interleukin-8; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D003907:Dexamethasone; D003094:Collagen