Bronchiolar and alveolar epithelial cell apoptosis in pulmonary fibrosis

肺纤维化中细支气管和肺泡上皮细胞凋亡

• 批准号: 09670620
• 负责人: KUWANO Kazuyoshi
• 金额: $ 2.18万
• 依托单位: KYUSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670620/
• 关键词: lung injury; pulmonary fibrosis; apoptosis; Fas抗原; Fasリガンド; カスパーゼ

Pulmonary fibrosis caused by tissue remodeling consisting of fibroblast proliferation, which is induced by bronchiolar and alveolar epithelial cell damage and prolongation of inflammation. We have examined the hypothesis that apoptosis of inflammatory cells and lung epithelial cells may be involved in this process. We described the abstract below. 1) DNA damage and p53 and p21 overexpression in lung epithelial cells from patients with IPF 2) Fas and FasL upregulation in lung epithelial cells and infiltrating lymphocytes, respectively, in lung epithelial cells from patients with IPF 3) Upregulation of p53, Fas, FasL in bleomycin-induced pneumopathy 4) Pulmonary fibrosis induced by inhalation of agonistic anti-Fas antibody 5) Fas- or FasL-deficient mice are resistant against bleomycin-induced pneumopathy 6) Amelioration of LPS- or bleomycin induced pneumopathy in mice by a caspase inhibitorThese results suggest that lung epithelial cell apoptosis is involved in the pathophysiology of pulmonary fibrosis.

肺纤维化是由细支气管和肺泡上皮细胞损伤和炎症延长引起的由成纤维细胞增殖组成的组织重塑引起的肺纤维化。我们研究了炎症细胞和肺上皮细胞凋亡可能参与这一过程的假设。我们在下面描述了摘要。1) IPF患者肺上皮细胞DNA损伤及p53、p21过表达2)IPF患者肺上皮细胞及浸润淋巴细胞Fas、FasL分别上调3)p53、Fas、吸入拮抗Fas抗体诱导的肺纤维化5 Fas-或FasL缺陷小鼠对博来霉素诱导的肺纤维化有抗性6 caspase抑制剂改善LPS-或博来霉素诱导的小鼠肺纤维化这些结果提示肺上皮细胞凋亡参与肺纤维化的病理生理。

项目成果

Kuwano K, Miyazaki H, Hagimoto N et al: "The involvement of Fas-Fas ligand pathway in fibrosing lung diseases."Am J Respir Cell Mol Biol. 20. 53-60 (1999)

Kuwano K、Miyazaki H、Hagimoto N 等人：“Fas-Fas 配体途径在纤维化肺疾病中的参与。”Am J Respir Cell Mol Biol。

萩本直樹 ら: "Induction of Apoptusis and Pulmonary fiberis in response to ligation of Fas antigen" Amerian Journal of Recpiratory Cell and Molecular Biology. 17. 272-278 (1997)

Naoki Hagimoto 等人：“Fas 抗原连接诱导细胞凋亡和肺纤维”，《美国呼吸细胞和分子生物学杂志》17. 272-278 (1997)。

Fujita M, Kuwano K, Kunitake R et al: "Endothelial cell apoptosis in lipopolysacch aride-induced lung injury in mice."Int Arch Allergy Immunol. 117. 202-208 (1999)

Fujita M、Kuwano K、Kunitake R 等人：“脂多糖诱导的小鼠肺损伤中的内皮细胞凋亡。”Int Arch Allergy Immunol。

Kaneko Y, Kuwano K, Hagimoto N et al: "Expression of B7-1, B7-2, and interleukin 12 in bleom ycin-induced pneumopathy in mice."Int Arch Allergy Immunol. 116. 306-312 (1999)

Kaneko Y、Kuwano K、Hagimoto N 等人：“B7-1、B7-2 和白细胞介素 12 在博莱霉素诱导的小鼠肺炎中的表达”。

Hagimoto N, Kuwano K, Kawasaki M et al: "Induction of interleukin-8 secretion and apoptosis in bronchiolar epithelial cells by Fas antigen"Am J Respir Cell Mol Biol. 21. 436-445 (1999)

Hagimoto N、Kuwano K、Kawasaki M 等人：“Fas 抗原诱导细支气管上皮细胞中白细胞介素 8 的分泌和凋亡”Am J Respir Cell Mol Biol。