Heo Kyung Wook, Park Seong Kook, Lee Yeo Myeong, Choe Si Hong, Gu Pyung Mo, Hong Tae Ui, Hur Dae Young
*Department of Otorhinolaryngology-Head and Neck Surgery †Department of Anatomy and Research Center for Tumor Immunology, Inje University Busan Paik Hospital, Busan, South Korea.
J Craniofac Surg. 2017 May;28(3):806-809. doi: 10.1097/SCS.0000000000003562.
Methotrexate (MTX) is very effective when used to treat chronic inflammatory diseases, and also induces apoptosis in nasal polyps (NPs). Increasing evidence suggests that Fas-Fas ligand (FasL) interactions activate multiple pathways involved in the regulation of immune and inflammatory cell functions. The aim of the present study was to identify pathways activated by Fas signaling when NPs were treated with MTX.
Nasal polyps tissues were cultured using an air-liquid interface organ culture method. Cultures were maintained in the absence or presence of MTX (10 or 100 μM) for 24 hours. The authors used the reverse transcription-polymerase chain reaction method and Western blotting to identify pathways activated by Fas when NPs were treated with MTX.
The Fas mRNA expression ratio was unchanged upon MTX treatment, but the FasL mRNA expression ratio was significantly higher in MTX-treated than nontreated polyps. In addition, the expression levels of the Fas and FasL proteins were significantly higher in polyps treated with both 10 and 100 μM MTX compared with nontreated polyps.
Methotrexate induces apoptosis in NPs via the Fas pathway. Future studies should explore the topical use of MTX for NP control. Methotrexate may be a useful alternative steroid-sparing agent for the treatment of NPs.
甲氨蝶呤(MTX)用于治疗慢性炎症性疾病时非常有效,且能诱导鼻息肉(NP)细胞凋亡。越来越多的证据表明,Fas - Fas配体(FasL)相互作用激活了参与免疫和炎症细胞功能调节的多种途径。本研究的目的是确定用MTX处理NP时Fas信号激活的途径。
采用气液界面器官培养法培养鼻息肉组织。培养物在不存在或存在MTX(10或100μM)的情况下维持24小时。作者使用逆转录 - 聚合酶链反应法和蛋白质印迹法来确定用MTX处理NP时Fas激活的途径。
MTX处理后Fas mRNA表达率未改变,但MTX处理的息肉中FasL mRNA表达率显著高于未处理的息肉。此外,与未处理的息肉相比,用10和100μM MTX处理的息肉中Fas和FasL蛋白的表达水平显著更高。
甲氨蝶呤通过Fas途径诱导鼻息肉细胞凋亡。未来的研究应探索MTX在局部控制鼻息肉方面的应用。甲氨蝶呤可能是一种用于治疗鼻息肉的有用的替代类固醇药物。