Korea University College of Medicine, Seoul, Korea.
Am J Rhinol Allergy. 2010 Sep-Oct;24(5):348-53. doi: 10.2500/ajra.2010.24.3520.
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.
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.
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.
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.
大环内酯类药物具有抗炎、免疫调节和组织修复作用。本研究旨在确定大环内酯类药物（红霉素[EM]和罗红霉素[RXM]）对转化生长因子（TGF）β1诱导的鼻息肉衍生成纤维细胞（NPDF）向肌成纤维细胞分化和细胞外基质积累的影响，并确定烟酰胺腺嘌呤二核苷酸磷酸氧化酶（Nox）4 和活性氧（ROS）是否参与上述过程。
在手术过程中获取了六名患者（三名女性和三名男性；32.3±5.2 岁）的鼻息肉，并从手术组织中分离出 NPDF。在 TGF-β1 诱导分化前，NPDF 先用大环内酯类药物预处理 2 小时。通过逆转录聚合酶链反应测定α-平滑肌肌动蛋白（SMA）、胶原 I 和 III 的 mRNA 表达，通过免疫细胞化学染色测定α-SMA 蛋白表达。通过 SirCol 胶原染色结合测定分析总胶原蛋白产生量。通过硝基四唑蓝还原测定法测量 ROS 活性，并通过荧光显微镜观察。
在 TGF-β1 诱导的 NPDF 中，EM 和 RXM 在 5 和 10μg/mL 浓度下显著抑制α-SMA 和胶原 I 和 III 的 mRNA 表达，并降低α-SMA 和胶原蛋白水平。在相同浓度下，EM 和 RXM 还抑制了 TGF-β1 诱导的 ROS 产生和 Nox4 mRNA 表达。
这些结果表明，EM 和 RXM 可能通过其抗氧化作用在抑制鼻息肉发展中发挥重要作用。
