TY - JOUR
T1 - The effect of macrolides on myofibroblast differentiation and collagen production in nasal polyp-derived fibroblasts
AU - Park, Hyo Hyun
AU - Park, Il Ho
AU - Cho, Jung Sun
AU - Lee, You Mi
AU - Lee, Heung Man
PY - 2010/9
Y1 - 2010/9
N2 - Background: Macrolides 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) beta1-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-beta1. 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-beta1-induced NPDFs, EM, and RXM significantly inhibited expressions of alpha-SMA and collagen types I and III mRNA and reduced alpha-SMA and collagen protein levels at concentrations of 5 and 10 μg/mL. EM and RXM also inhibited TGF-β1-induced ROS production and Nox4 mRNA expression at the same concentrations. Conclusion: These results suggest the possibility that EM and RXM may play an important role in inhibiting the development of nasal polyps through their antioxidant effect.
AB - Background: Macrolides 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) beta1-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-beta1. 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-beta1-induced NPDFs, EM, and RXM significantly inhibited expressions of alpha-SMA and collagen types I and III mRNA and reduced alpha-SMA and collagen protein levels at concentrations of 5 and 10 μg/mL. EM and RXM also inhibited TGF-β1-induced ROS production and Nox4 mRNA expression at the same concentrations. Conclusion: These results suggest the possibility that EM and RXM may play an important role in inhibiting the development of nasal polyps through their antioxidant effect.
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U2 - 10.2500/ajra.2010.24.3520
DO - 10.2500/ajra.2010.24.3520
M3 - Article
C2 - 21244734
AN - SCOPUS:77957585319
SN - 1945-8924
VL - 24
SP - 348
EP - 353
JO - American Journal of Rhinology and Allergy
JF - American Journal of Rhinology and Allergy
IS - 5
ER -