New pathogenesis and therapeutic : strategy for diffuse panbronchiolitis by regulation of intracellular apoptotic molecules

新的发病机制和治疗：通过调节细胞内凋亡分子治疗弥漫性全细支气管炎的策略

• 批准号: 13670605
• 负责人: KADOTA Jun-ichi
• 金额: $ 1.79万
• 依托单位: Oita University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670605/
• 关键词: diffuse panbronchiolitis; apoptosis; Bax; Bcl-2; caspase; macrolide antibiotics; Pseudomonas aeruginosa; biofilm; サイトカイン; twitching motility; リンパ球; マクロライド抗菌薬; caspase3; Fas; Fas ligand; TUNEL法; Flowcytometry

1)No immunostain of Bax was observed in lymphocytes around respiratory bronchioles of diffuse panbronchiolitis (DPB), while Bcl-2 was stained in the majority of the lymphocytes. Furthermore, apoptosis-inducing enzyme, caspase 3 was also unstained. This indicates that over expression of Bcl-2 protein plays an important role in suppression of lymphocyte apoptosis in DPB.2)14- or 15-membered ring macrolide antibiotics at 100 mg/l induced apoptosis of CD3/CD28-activated lymphocytes obtained from healthy volunteers through downregulation of anti-apoptotic protein, Bcl-xL. This suggest that macrolides influence intracellular signal, especially anti-apoptotic protein.3)In a murine model with chronic Pseudomonas aeruginosa infection, 80-day administration of 14-membered macrolide antibiotic, erythromycin inhibited the biofilm formation of P.aeruginosa followed by elimination of the bacteria. This is a first report, indicating in vivo that long-term treatment of macrolides can eliminate the bacteria through destruction of biofilm formation.

（1）弥漫性泛细支气管炎（DPB）呼吸性细支气管周围淋巴细胞Bax免疫染色阴性，Bcl-2免疫染色阳性。此外，凋亡诱导酶半胱天冬酶3也未染色。这表明Bcl-2蛋白的过表达在DPB中淋巴细胞凋亡的抑制中起重要作用。2）100 mg/l的14-或15-元环大环内酯类抗生素通过下调抗凋亡蛋白Bcl-xL诱导从健康志愿者获得的CD 3/CD 28活化的淋巴细胞的凋亡。这表明大环内酯类药物影响细胞内信号，尤其是抗凋亡蛋白。3）在慢性铜绿假单胞菌感染的小鼠模型中，给予14元大环内酯类抗生素红霉素80天抑制铜绿假单胞菌生物膜形成，随后消除细菌。这是第一份报告，表明在体内，大环内酯类药物的长期治疗可以通过破坏生物膜的形成来消除细菌。

项目成果

Yanagihara K: "Role of elastase in a mouse model of chronic respiratory Pseudomonas aeruginos a infection that mimics diffuse panbronchiolitis"J Med Microbiol. 52. 531-535 (2003)

Yanagihara K：“弹性蛋白酶在慢性呼吸道铜绿假单胞菌（一种模仿弥漫性全细支气管炎的感染）小鼠模型中的作用”J Med Microbiol。

門田 淳一: "びまん性汎細気管支炎は克服されたか"Mebio.. 18(9). 89-93 (2001)

Junichi Kadota：“弥漫性全细支气管炎已被克服吗？” Mebio.. 89-93 (2001)。

Clarithromycin and azithromycin induce apoptosis of activated lymphocytes via down-regulation of Bcl-xL

• DOI: 10.1016/j.intimp.2004.05.011
• 发表时间: 2004-09-01
• 期刊: INTERNATIONAL IMMUNOPHARMACOLOGY
• 影响因子: 5.6
• 作者: Mizunoe, S;Kadota, J;Nasu, M
• 通讯作者: Nasu, M

Kadota J: "Long-term efficacy and safety of clarithromycin treatment in patients with diffuse panbronchiolitis"Respir Med. 97. 844-850 (2003)

Kadota J：“克拉霉素治疗弥漫性全细支气管炎患者的长期疗效和安全性”Respir Med。

門田 淳一: "炎症細胞動態からみたびまん性汎細気管支炎"感染症と化学療法. 5. 1-4 (2001)

Junichi Kadota：“从炎症细胞动力学观察弥漫性全细支气管炎”《传染病与化疗》，5. 1-4 (2001)。