Department of Otolaryngology-Head and Neck Surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.
Department of Otolaryngology-Head and Neck Surgery, Maryknoll Medical Center, Busan, Korea.
Clin Exp Otorhinolaryngol. 2014 Jun;7(2):112-8. doi: 10.3342/ceo.2014.7.2.112. Epub 2014 May 21.
Glucocorticoids, such as dexamethasone (DEX), increase apoptosis in a variety of white cells in nasal polyps and apoptosis is an important factor in the resolution of inflammation. However, the mechanism of glucocorticoids induced apoptosis in nasal polyp remains unclear. In this study the authors evaluated which pathways were engaged in apoptosis induced by DEX in an ex vivo model of nasal polyps.
Nasal polyp tissues were cultured using an air-liquid interface method. Cultures were maintained in the absence or presence of DEX (10 or 100 µM) for 24 hours. To investigate the involvement of the apoptotic signaling pathways in nasal polyp, such as caspase cascades, Fas-FasL signaling pathway, mitochondrial pathway and p38 mitogen-activated protein kinase (MAPK)/JNK pathway, the authors performed reverse transcription-polymerase chain reaction and Western blotting.
The expression ratios of FasL, activated form of caspase-8, caspase-9, and caspase-3 were significantly higher in DEX-treated polyps (P<0.01). In the Bcl-2 family expression, the anti-apoptotic molecules, Bcl-2 and Bcl-XL decreased, but pro-apoptotic molecules, Bax increased, and Bid and Bad were activated. In the conventional MAPKs, JNK, and the phospho-p38 MAPK were significantly higher, but phospho-extracellular signal-regulated kinase (ERK)1/2 was significantly lower in DEX-treated polyps (P<0.01).
DEX induces apoptosis of nasal polyp via caspase cascades, Fas-FasL signaling pathway, mitochondrial pathway and p38 MAPK/JNK pathway.
地塞米松（DEX）等糖皮质激素可增加鼻息肉中多种白细胞的凋亡，而凋亡是炎症消退的一个重要因素。然而，糖皮质激素诱导鼻息肉细胞凋亡的机制尚不清楚。本研究旨在评估DEX 在鼻息肉的离体模型中诱导凋亡所涉及的途径。
采用气-液界面培养法培养鼻息肉组织。在无 DEX（10 或 100μM）或有 DEX 的条件下培养 24 小时。为了研究凋亡信号通路（如半胱天冬酶级联、Fas-FasL 信号通路、线粒体途径和 p38 丝裂原活化蛋白激酶（MAPK）/JNK 途径）在鼻息肉中的作用，作者进行了逆转录-聚合酶链反应和 Western blot 分析。
DEX 处理的息肉中 FasL、活化的 caspase-8、caspase-9 和 caspase-3 的表达比值明显升高（P<0.01）。在 Bcl-2 家族表达中，抗凋亡分子 Bcl-2 和 Bcl-XL 减少，而促凋亡分子 Bax 增加，Bid 和 Bad 被激活。在经典的 MAPKs 中，JNK 和磷酸化 p38 MAPK 明显升高，而磷酸化 ERK1/2 明显降低（P<0.01）。
DEX 通过半胱天冬酶级联、Fas-FasL 信号通路、线粒体途径和 p38 MAPK/JNK 途径诱导鼻息肉细胞凋亡。
