The effect of macrolides on myofibroblast differentiation and collagen production in nasal polyp-derived fibroblasts

Background: Macro tides are known to have anti-inflammatory, immunomodulatory, and tissue reparative effects. The purpose of this study was to determine the effect of macrolides (erythromycin [EM] and roxithromycin [RXM]) on the differentiation of fibroblasts into myofibroblasts and extracellular matrix accumulation in transforming growth factor (TGF) betal induced nasal polyp derived fibroblasts (NPDFs) and to determine if NADPH oxidase (Nox) 4 and reactive oxygen species (ROS) are involved in the aforementioned processes. Methods: Nasal polyps of six patients (three women and three men; 32.3 +/- 5.2 years of age) were acquired during surgery and NPDFs were isolated from surgical tissues. NPDFs were pretreated with macrolides for 2 hours before differentiation induction by TGF-betal. The mRNA expressions of alpha-smooth muscle actin (SMA), collagen types I and III, and Nox4 were determined by reverse-transcription polymerase chain reaction, and the expression of alpha-SMA protein was determined by immunocytochemical staining. The amount of total collagen production was analyzed by SirCol collagen dye-binding assay. ROS activity was measured by nitroblue tetrazolium reduction assay and was visualized by fluorescent microscopy. Results: In TGF-betal induced NPDFs, EM, and RXM significantly inhibited expressions of alpha-SMA and collagen types land III mRNA and reduced alpha-SMA and collagen protein levels at concentrations of 5 and 10 mu g/mL. EM and RXM also inhibited TGF-beta 1-induced ROS production and Nox4 mRNA expression at the same concentrations. Conclusion: These results suggest the possibility that EM and R)CM may play an important role in inhibiting the development of nasal polyps through their antioxidant effect. (Am J Rhinol Allergy 24, 348-353, 2010; doi: 10.2500/ajra.2010.24.3520)