Molecular mechanisms of airway mucus hypersecretion and airway clearance dynfunction induced by long-acting beta-2 agonist

长效β2激动剂引起气道粘液分泌过多和气道清除功能障碍的分子机制

• 批准号: 23591127
• 负责人: TAMAOKI Jun
• 金额: $ 3.24万
• 依托单位: Tokyo Women's Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591127/
• 关键词: 気道クリアランス; 粘液線毛輸送; 気道上皮細胞; 線毛運動; β2受容体; 気道上皮; 細胞増殖; 粘液分泌; 喘息; β２刺激薬; リモデリング; 上皮成長因子受容体; ERKカスケード; チロシンリン酸化

Stimulation of mouse tracheal epithelial cells with the long-acting beta-2 agonist salmeterol increased DNA and protein synthesis in a concentration-dependent manner, an effect that was abolished in the presence of a specific beta-2 receptor antagonist. Salmeterol also induced phosphorylation of EGFR and upregulated the expression of MUC5AC in cultured tracheal epithelial cells, and these effects were significantly inhibited by a EGFR tyrosine kinase inhibitor and transfection of dominant negative mutant of H-Ras, indicating that Ras-ERK cascade may be involved in the salmeterol-induced cell responses. Moreover, salmeterol increased mucociliary transport rate from the carina toward oropharynx in the mouse airway. Ciliary beat frequency of tracheal epithelial cells determined by a photoelectric method was increased in response to salmeterol. These findings suggest that simulation of airway epithelial cells with long-acting beta-2 agonist causes an improvement of airway clearance.

用长效β-2激动剂salmeterol刺激小鼠气管上皮细胞以浓度依赖性的方式增加了DNA和蛋白质合成，这种作用在存在特定β-2受体拮抗剂的情况下被废除了。盐美分析还诱导了EGFR的磷酸化，并上调了MUC5AC在培养的气管上皮细胞中的表达，这些作用受到EGFR酪氨酸激酶抑制剂的显着抑制，并转染H-RAS的主要阴性突变体的转染，表明Ras-erk cascade cascade cascade cascade cascade cascade canscade canscade cascace canscade cascace canscade canscade cascace cascace casc casc castcade cascace cascace casc casc casc cascace cascace cascace casc casc castcade可能涉及盐含量响应。此外，沙美醇提高了小鼠气道中从Carina到口咽的粘膜纤毛运输速率。通过光电法确定的气管上皮细胞的睫状频率对莎梅特醇的响应增加。这些发现表明，具有长效β-2激动剂的气道上皮细胞的模拟会改善气道通关。

项目成果

鼻炎合併喘息の病態と治療：one airway, one diseaseの観点から

哮喘并发鼻炎的病理及治疗：从一种气道、一种疾病的角度

• 发表时间: 2013
• 作者: Arimura K;Aoshiba K;Tsuji T;Tamaoki J;Tamaoki J;Tamaoki J;玉置淳;玉置淳
• 通讯作者: 玉置淳

Effect of tiotropium on mucus hypersecretion and their impact and nasal mucociliary clearance in patients with COPD

噻托溴铵对 COPD 患者粘液过度分泌及其影响和鼻粘液纤毛清除能力的影响

• 作者: Tagaya E;Tamaoki J;Kirishi S;Isono K;Nagaoka M;Kimura N;Kondo M;Nagai A
• 通讯作者: Nagai A

Regulation of airway cleaning in inflammatory airway diseases

炎症性气道疾病中气道清洁的调节

• 发表时间: 2013
• 作者: Kondo M;Nakata J;Arai N;Izumo T;Takeyama K;Tamaoki J;Nagai A;玉置淳;玉置淳;玉置淳;玉置淳;玉置淳;玉置淳;切士紗織,多賀谷悦子,寺西香織,溝渕莉恵,久保綾子,石井成伸,武山廉,磯野一雄,近藤光子,玉置淳;近藤光子,新井尚希,有村健,中田潤子,多賀谷悦子,武山廉,玉置淳;辻真世子,森島正,清水一彦,北原秀治,玉置淳,久米努,江崎太一;Tamaoki J
• 通讯作者: Tamaoki J

Nagai Effect of tiotropium on mucus hypersecretion and their impact and nasal mucociliary clearance in patients with COPD

Nagai 噻托溴铵对 COPD 患者粘液过度分泌及其影响和鼻粘膜纤毛清除率的影响

• 发表时间: 2012
• 作者: Tagaya E;Tamaoki J;Kirishi S;Isono K;Nagaoka M;Kimura N;Kondo M
• 通讯作者: Kondo M

風邪症候群と関連疾患:気管・気管支炎,肺炎.ENT臨床フロンティアシリーズ

寒证及相关疾病：气管/支气管炎、肺炎。耳鼻喉科临床前沿系列

• 发表时间: 2013
• 作者: Kondo M;Nakata J;Arai N;Tagaya E;Takeyama K;Tamaoki J (ed;Tamaoki J);玉置淳,八木理充,落合克律 (小林俊光,高橋晴雄,浦野正美編)
• 通讯作者: 玉置淳,八木理充,落合克律 (小林俊光,高橋晴雄,浦野正美編)