154 A 26-Week Study Evaluating the Safety and Efficacy of Ciclesonide Hydrofluoralkane Nasal Aerosol in Subjects With Perennial Allergic Rhinitis

153 Effect of Simvastatin on Transforming Growth Factor BETA-1Induced Myofibroblast Differentiation and Collagen Production in Nasal Polyp-Derived Fibroblasts Il-Ho Park, MD, and Heung-man Lee, MD, PhD. Department of otorhinolaryngology-head and neck surgery, Korea university college of medicine, Seoul, South Korea. Background: Statins are the most commonly prescribed drugs for the treatment of hypercholesterolemia. Statins exert not only lipid-lowering but also other cellular effects, including anti-fibrotic properties. The purposes of this study were to determine the effect of simvastatin on Transforming growth factor (TGF)-b1-induced myofibroblast differentiation and collagen production in nasal polyp-derived fibroblasts (NPDFs) and to verify the mechanism of the effect of simvastatin in TGF-b1-induced myofibroblast differentiation in NPDFs. Methods: NPDFs were pre-treated with simvastatin with or without mevalonate or Y-27643 for 2 hours prior to induction by TGF-b1. The expression of a-smooth muscle actin (SMA) and collagen type IV mRNA was determined by a reverse transcription-polymerase chain reaction, and the expression of a-SMA protein was determined by immunofluoescent cytochemical staining. Total soluble collagen production was analyzed by the SirCol collagen dye-binding assay. Phosphorylation of Smad 2/3 was evaluated by Western blot analysis. Results: In TGF-b1-induced NPDFs, simvastatin significantly inhibited the expressions of a-SMA and collagen type IV mRNA and reduced a-SMA and collagen protein levels. Pre-treatment with mevalonate reversed the effect of simvastatin. The expression of a-SMA mRNA and protein was significantly decreased by pre-treatment with Y-27632. The TGF-b1-induced expression of pSmad 2/3 protein was notably decreased by pre-treatment with simvastatin. Conclusions: We showed that simvastatin inhibits TGF-b1-induced myofibroblast differentiation (expression of a-SMA) and collagen production in NPDFs and Rho/Rock and TGF-b/Smad signaling is involved as an underlying mechanism. The results of our study suggest that simvastatin is a possible candidate for the suppression of nasal polyp formation.