Myofibroblasts in Nasal Polyposis: Regulation by Topical Steroids

Abstract

OBJECTIVES: To compare numbers of myofibroblasts, a fibroblast phenotype associated with chronically inflamed tissue, in nasal polyp tissues from untreated and corticosteroid-treated subjects. To study whether corticosteroids can directly affect myofibroblast differentiation in vitro.PATIENTS AND METHODS: Immunolocalization of alpha-smooth muscle actin (alpha-SMA) as a marker of myofibroblast differentiation, vimentin and transforming growth factor (TGF)-beta in nasal polyp tissues from nine patients who had taken no steroids for at least a month before polypectomy and from eight patients who had received intranasal budesonide or beclomethasone dipropionate continuously for four to 12 months before polypectomy. Cultured nasal polyp fibroblasts were exposed to budesonide for six days and alpha-SMA expression was determined by immunocytochemistry.RESULTS: Nasal polyp tissues from untreated subjects were characterized by the presence of a substantial number of myofibroblasts compared with tissues from corticosteroid-treated subjects. The median percentages of alpha-SMA positive cell areas per total area for the two groups were 6.4% (0.5 to 11.5) and 1.3% (0.1 to 4.7), respectively. This difference in alpha-SMA staining between the two groups was not due to a decrease in fibroblast numbers (vimentin-positive spindle-shape cells). Numbers of TGF-beta positive cells were similar in the two groups of subjects. In vitro, budesonide treatment decreased the number of alpha-SMA positive fibroblasts in primary lines in a dose dependent manner.CONCLUSIONS: The difference in myofibroblast numbers between nasal polyp tissues from untreated and corticosteroid-treated subjects, as shown by immunolocalization of alpha-SMA, suggests a new therapeutic effect of nasal topical corticosteroids in nasal polyposis. This could be a direct effect of the drug on fibroblast differentiation and/or modulation of cytokine production.