The effect of transforming growth factor (TGF)-β1 and (TGF)-β2 on nasal polyp fibroblast activities involved upper airway remodeling: Modulation by fluticasone propionate
Abstract
Transforming growth factor (TGF)-beta may play a significant role in nasal polyposis pathogenesis, possibly through fibroblast activation. We studied the effects of two TGF-beta isoforms (TGF-beta1 and TGF-beta2) on nasal polyposis fibroblasts by evaluating cell proliferation and differentiation into myofibroblasts. In addition, the inhibitory activity of different concentrations of fluticasone propionate (F.P.) was tested in this in vitro system. Primary nasal polyp tissue-derived fibroblasts were stimulated with different concentrations (1, 10 and 20 ng/ml) of TGF-beta1 and TGF-beta2 for different incubation periods (24, 48 and 72 h) and cell proliferation [3H thymidine ([3H]TdR) incorporation] and alpha-smooth muscle actin (alpha-SMA) expression (immunocytochemistry) was evaluated. The lowest concentration of TGF-beta1 (1 ng/ml) induced a significant increase in [3H]TdR incorporation at 48 and 72 h (p<0.05, each comparison), while in the presence of TGF-beta (10 ng/ml) and TGF-beta2 (1 ng/ml) the enhancement in cell proliferation was significant only after 48 h (p<0.05, each comparison with the unstimulated cells). In contrast, a significant increase in alpha-SMA expression was observed in the presence of the two highest concentration of both TGF-beta isoforms, at 48 and 72 h for TGF-beta1 (p<0.05, each comparison), but only at 72 h for TGF-beta2 (<0.05, each comparison). Finally, at all concentrations tested, F.P. significantly inhibited the TGF-beta1 and TGF-beta2-induced 3HTdR incorporation (p<0.01, each comparison) and the alpha-SMA expression (p<0.05, each comparison). Thus, in vitro different concentrations of TGF-beta1 and TGF-beta2 appear to sequentially stimulate primary nasal polyp tissue-derived fibroblast proliferation and myofibroblast differentiation. These activities are effectively inhibited by F.P.
Key Biomarkers
Symptom Clusters
References (5)
- Nasal polyposis: an updateCurrent Opinion in Allergy and Clinical Immunology · 2003
- Expression of the Transforming Growth Factor β Isoforms in Inflammatory Cells of Nasal PolypsArchives of Otolaryngology - Head and Neck Surgery · 1998
- Eosinophil expression of transforming growth factor-beta and its receptors in nasal polyposis: role of the cytokines in this disease processAmerican Journal of Otolaryngology · 1997
- Transforming Growth Factor β1 in Nasal Remodeling: Differences between Chronic Rhinosinusitis and Nasal PolyposisAmerican Journal of Rhinology · 2004
- Expression of transforming growth factor-beta 1 and alpha-smooth muscle actin of myofibroblast in the pathogenesis of nasal polypsKaohsiung J med Sci · 2001
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