Study on molecular mechanisms of development of interstitial pneumonia

间质性肺炎发生发展的分子机制研究

基本信息

批准号：
15390258
负责人：
FUKUDA Takeshi
金额：
$ 9.41万
依托单位：
Dokkyo Medical University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

项目摘要

It has already been reported that the helper lymphocyte takes part in the lung fibrosis after interstitial pneumonia develops. Recently, the role is not clear though it is reported that leukotrien C4 (LTC4)is alsoinvolved in the lung fibrosis. Then, to develop the treatment of interstitial pneumonia and the fibroid, and to establish it, we analyzed the influence of the airway inflammation induced by activation of lymphocytes and LTC4 give to the bleomycin-induced lung fibrosis. To this end, LTC4 synthesis enzyme gene (LTC4S) transgenic (Tg) mice and wild type mice were sensitized with ovalbumin (OVA)/alum. We analyzed the effects of antigen-induced inflammation and LTC4 on bleomycin-induced lung fibrosis.The airway inflammation mainly composed of the lymphocytes and the eosinophils after an exposure of OVA alone was reinforced in the LTC4S-Tg mouse compared with the wild type mouse. Production of Th2 cytokines (IL- 4,IL-13) and TGF-β in a bronchial alveolar lavage fluid (BALF) was augmented in LTC4S-Tg mouse more than wild type mice. The OVA-induced airway inflammation with an increases in TGF-β was further augmented by a simultaneous exposure of bleomycin in both LTC4S-Tg mice and wild type mice, and the extent was especially stronger in the LTC4S-Tg mice.These results indicated a possibility that the airway inflammation after the antigen may promote and accelerate the bleomycin-induced lung fibrosis. Althouh its mechanism remains unclear, antigen-induced productions of Th2 cytokine and TGF-β may be involved in the airway inflammation. Furthermore, since LTC4S-Tg mice compared with the wild type mice showed the reinforcement of the inflammation and the cytokine productions, it is possible that LTC4 aggravates belomyin-induced lung fibrosis through promoting directly and/or indirectly the Th2 cytokines and TGF-β. A histological examination is now in progress to confirm the influence LTC4 and antigen-induced response on bleomycin-induced lung fibrosis.

据报道，间质性肺炎发育后，辅助淋巴细胞参与肺纤维化。最近，尽管据报道白细胞C4（LTC4）也参与了肺纤维化，但尚不清楚该作用。然后，为了开发肺炎和肌瘤的治疗，并确定它，我们分析了通过激活淋巴细胞激活而引起的气道注射的影响，而LTC4给出了博来霉素诱导的肺纤维化。为此，LTC4合成酶基因（LTC4S）转基因（TG）小鼠和野生型小鼠对卵巢蛋白（OVA）/明矾敏感。我们分析了抗原诱导的感染和LTC4对博来霉素诱导的肺纤维化的影响。与与野生型小鼠相比，在LTC4S-TG-TG小鼠中，仅在LTC4S-TG小鼠中加强了卵A的炎症，主要由淋巴细胞组成和嗜酸性嗜酸菌。与野生型小鼠相比，在LTC4S-TG小鼠中增强了支气管肺泡灌洗液（BALF）中Th2细胞因子（IL-4，IL-13）和TGF-β。通过在LTC4S-TG小鼠和野生型小鼠中简单地暴露博霉素，可以进一步增强OVA诱导的气道注射，并增加TGF-β的增加，而LTC4S-TG小鼠中的程度尤其强大。这些结果表明，抗原后的气道炎症可能会促进和加速博来霉素诱导的肺纤维化。尽管其机制尚不清楚，但抗原诱导的Th2细胞因子和TGF-β的生产可能参与气道注射。此外，由于LTC4S-TG小鼠与野生型小鼠相比表明感染和细胞因子产生的增强，因此LTC4可能通过直接和/或间接促进Th2细胞因子和TGF-β加剧了Belomyin诱导的肺纤维化。现在正在进行组织学检查，以确认LTC4的影响和抗原诱导的对博来霉素诱导的肺纤维化的反应。