Modulation of mucus production by interleukin-13 receptor α2 in the human airway epithelium
Modulation of mucus production by interleukin-13 receptor α2 in the human airway epithelium
复制标题
DOI：
10.1111/j.1365-2222.2007.02871.x
复制
发表时间：
2008-01-01
影响因子：
6.1
通讯作者：
Yamaya, M.
中科院分区：
文献类型：
--
作者：
Tanabe, T.;Fujimoto, K.;Yamaya, M.
IL-13诱导气道上皮细胞杯状细胞增生和粘液过量产生。IL-13受体α 2 （IL-13R α(2)）被认为通过抑制IL-13信号在气道上皮中充当“诱饵受体”。然而，IL-13R α(2)对粘液产生的调节机制尚不清楚。目的探讨白细胞介素- 13r α(2)在杯状细胞增生和白细胞介素-13分泌粘液过量中的作用。方法从肺癌或良性肺肿瘤行肺切除术的患者中获取支气管。采用气液界面法分离培养正常人支气管上皮细胞（NHBECs）。结果在NHBECs中加入IL-13后，PAS阳性细胞、杯状细胞和muc5ac阳性细胞数量增加。添加IL-13后，上清液中MUC5AC蛋白浓度和MUC5AC mRNA表达量显著升高，21 d时恢复到对照水平。IL-13R α (2) mRNA表达在第7天显著升高，随后持续升高至第21天。在第14和21天，上清液中IL-13R α(2)的可溶性蛋白显著增加。抗IL-13R α(1)抗体和重组IL-13R α(2)抗体减少pas阳性细胞、杯状细胞和MUC5AC阳性细胞的数量和MUC5AC mRNA的数量，而抗IL-13R α(2)抗体增加这些细胞的数量和MUC5AC mRNA的数量。通过抗IL-13R α(1)抗体和重组IL-13R α(2)降低IL-13诱导上清MUC5AC蛋白的浓度。抗IL-13R α(1)抗体和重组IL-13R α(2)抑制il -13诱导的信号转导和转录激活因子（STAT）的激活。相比之下，重组IL-13R α不抑制il -4诱导的粘液产生、粘液分泌和STAT激活(2)。结论IL-13R α(2)的可溶性形式可能通过包括IL-13R α(1)在内的NHBECs通路，通过IL-13调节黏液过量产生。
Background IL-13 induces goblet cell hyperplasia and mucus overproduction in airway epithelial cells. IL-13 receptor alpha 2 (IL-13R alpha(2)) has been suggested to act as a 'decoy receptor' in the airway epithelium by inhibiting the IL-13 signal. However, the regulatory mechanisms for mucus production by IL-13R alpha(2) remain unclear.Objective The aim of this study was to examine the role of IL-13R alpha(2) in goblet cell hyperplasia and mucus overproduction by IL-13.Methods Bronchi were obtained from patients who underwent a lung resection due to lung cancer or benign lung tumours. Normal human bronchial epithelial cells (NHBECs) were isolated and cultured using an air-liquid interface (ALI) method.Results The number of periodic acid-Schiffs (PAS)-positive cells, goblet cells and MUC5AC-positive cells increased after adding IL-13 into NHBECs. The concentrations of MUC5AC protein in the supernatant and the mRNA expression of MUC5AC significantly increased after adding IL-13, and returned to control levels at 21 days. The mRNA expression of IL-13R alpha(2) significantly increased at 7 days and then continuously increased up to 21 days. The protein of a soluble form of IL-13R alpha(2) in the supernatants significantly increased at 14 and 21 days. Anti-IL-13R alpha(1) antibody and recombinant IL-13R alpha(2) reduced the number of PAS-positive cells, goblet cells and MUC5AC-positive cells, and MUC5AC mRNA, while the anti-IL-13R alpha(2) antibody increased the number of these cells and MUC5AC mRNA. The concentration of MUC5AC protein in the supernatant induced by IL-13 was reduced by anti-IL-13R alpha(1) antibody and recombinant IL-13R alpha(2). IL-13-induced signal transducer and activator of transcription (STAT) activation was inhibited by anti-IL-13R alpha(1) antibody and recombinant IL-13R alpha(2). In contrast, the IL-4-induced mucus production, mucus secretion and STAT activation were not inhibited by recombinant IL-13R alpha(2).Conclusion The soluble form of IL-13R alpha(2) may therefore modulate mucus overproduction by IL-13 through the pathway including IL-13R alpha(1) in NHBECs.