Protective mechanisms in inflammatory lung diseases at airway and alveolar area

气道和肺泡区炎症性肺部疾病的保护机​​制

• 批准号: 12670557
• 负责人: NAGAI Sonoko
• 金额: $ 1.6万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670557/
• 关键词: interstitial pneumonia; collagen-vascular disease; fibroblast; cytokine; protease; T-lymphocyte; TGFB; apoptosis; 気道および肺胞領域; 免疫反応・炎症反応; Th1リンパ球; Th2リンパ球; Th3リンパ球

We investigated on the pathogenesis of inflammatory lung diseases (interstitial pneumonias) using clinical samples, aiming at progressive or protective cytokine profiles and protease-antiprotease imbalance. We scored histopathological findings of lung specimens obtaind from 31 cases (16 IPF, 9 CVD other than SSc and 6 SSc) using a semiquaqntitative scoring method. Fewer macrophages in the alveolar spaces and a decrease in the degree of fibrosis may contribute to BALF lymphocytosis more in patients with in the degree of fibrosis may contribute to BALF lymphocytosis more in patients with UIP/CVD non-SSc than in patients with IPF/UIP and UIP-SSc. We examined mRNA expressions of MMP-3 and TIMP-3 in a cell line (A549) and in primary culture of normal adult human type II pneumocytes using RT-PCR. The matrix degradation is enhanced by IL-1beta and suppressed by TGF-betal via regulations in the balance between MMP-3 and TIMP-3. We investigated the cytotoxic effects of cigarette smoke extract ( … More CSE) on an alveolar type II cell-derived cell line (A549). Apoptosis of alveolar epithelial cells may be one of the mechanisms of lung injuury induced by cigarette smoking. This cytotoxic effect might be due to an interaction between aldehydes and oxidants present in CSE or formed in CSE-exposed cells. We compared the function of lung fibroblasts obtained from surgically biopsied cells. We compared the function of lung fibroblasts obtained from surgically biopsied specimens of patients with UIP (n=5), NSIP (n=5), and normal control (n=5). Fibroblasts obtained from UIP showed increased contractility compared with those obtained from NSIP or controls with enhanced F-action content in fibroblasts. The products representing the contractility were identified as fibronectin (ED-A domain) and TGF-betal by immunoblots. The contractility positively korrelated with the amount of either fibronectin or TGF-beta 1. Thus, UIP fibroblasts showed greater contractility than did NSIP fibroblasts or TGF-beta 1. Thus, UIP fibroblasts showed greater contractility than did NSIP fibroblasts and up-regulated control fibroblasts. Less

我们使用临床样本研究了炎性肺病（间质性肺炎）的发病机制，目的是进行性或保护性细胞因子谱和蛋白酶-抗蛋白酶失衡。我们对31例（16例IPF，9例非SSc CVD和6例SSc）的肺组织病理学检查结果进行了半定量评分。肺泡腔中巨噬细胞减少和纤维化程度降低可能导致UIP/CVD非SSc患者的BALF淋巴细胞增多，而纤维化程度降低可能导致UIP/CVD非SSc患者的BALF淋巴细胞增多，而IPF/UIP和UIP-SSc患者的BALF淋巴细胞增多。我们用RT-PCR检测了MMP-3和TIMP-3在细胞系（A549）和正常成人II型肺细胞原代培养中的mRNA表达。通过调节MMP-3和TIMP-3之间的平衡，IL-1 β可增强基质降解，TGF-β 1可抑制基质降解。我们研究了香烟烟雾提取物的细胞毒性作用（ ...更多信息 CSE）对肺泡II型细胞衍生的细胞系（A549）的作用。肺泡上皮细胞凋亡可能是吸烟致肺损伤的机制之一。这种细胞毒性作用可能是由于醛和氧化剂之间的相互作用存在于CSE或在CSE暴露的细胞中形成。我们比较了从手术活检细胞中获得的肺成纤维细胞的功能。我们比较了从UIP（n=5）、NSIP（n=5）和正常对照（n=5）的手术活检标本中获得的肺成纤维细胞的功能。从UIP获得的成纤维细胞显示出增加的收缩性相比，从NSIP或控制与增强的F-作用含量的成纤维细胞。代表收缩性的产物通过免疫印迹鉴定为纤连蛋白（ED-A结构域）和TGF-β 1。收缩力与纤维连接蛋白或TGF-β 1的含量呈正相关。因此，UIP成纤维细胞比NSIP成纤维细胞或TGF-β 1表现出更大的收缩性。因此，UIP成纤维细胞显示出比NSIP成纤维细胞和上调的对照成纤维细胞更大的收缩性。少

项目成果

Miki H, Nagai S et al.: "Fibroblast contractility : usual interstitial pneumonia and nonspecific interstitial promotion"Am J Respir Chit Care Med.. 162. 2259-2264 (2000)

Miki H、Nagai S 等人：“成纤维细胞收缩性：普通间质性肺炎和非特异性间质性促进”Am J Respir Chit Care Med.. 162. 2259-2264 (2000)

Hoshino Y, Nagai S et al.: "Cytotoxic effects of cigarette smoke. extract on an alveolar type II cell-derived cell line"Am J Physiol Lung Cell Mol Physiol.. 281. 509-516 (2001)

Hoshino Y、Nagai S 等：“香烟烟雾提取物对肺泡 II 型细胞衍生细胞系的细胞毒性作用”Am J Physiol Lung Cell Mol Physiol.. 281. 509-516 (2001)

Nagai S et al.: "Heterogeneity of pulmonary fibrosis : interstitial pneumonias and sarcoidosis"Curr Opin Pulm Med.. 7. 262-271 (2001)

Nagai S 等：“肺纤维化的异质性：间质性肺炎和结节病”Curr Opin Pulm Med.. 7. 262-271 (2001)

Miki H, Nagai S et al.: "Gluco coticoid-induced contractility and F-actin content of human lung fibroblasts in three dimensional culture"Am J Physiol Lung Cell Mol Physiol. 278. 13-18 (2000)

Miki H、Nagai S 等人：“三维培养物中葡萄糖皮质激素诱导的人肺成纤维细胞的收缩性和 F-肌动蛋白含量”Am J Physiol Lung Cell Mol Physiol。

Miki H., Nagai S., et. al.: "Gluco conticoid-induced contractivity and F-actin contest of human lung fibroblasts in three dimentional culture"Am J Physiol Lung Ceil Mol Physiol. 278. 13-18 (2000)

Miki H.，Nagai S.，等。