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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.

已有文献报道，间质性肺炎发生后，辅助淋巴细胞参与了肺纤维化。近年来，虽然有报道白三烯C4（LTC4）也参与肺纤维化，但其作用尚不清楚。然后，为了开发间质性肺炎和纤维瘤的治疗，并建立它，我们分析了由淋巴细胞和LTC4活化诱导的气道炎症对博莱霉素诱导的肺纤维化的影响。为此，用卵清蛋白（OVA）/明矾致敏LTC4合成酶基因（LTC4S）转基因（Tg）小鼠和野生型小鼠。我们分析了抗原诱导的炎症反应和LTC4对博莱霉素诱导的肺纤维化的影响，与野生型小鼠相比，单独暴露于OVA后，LTC4S-Tg小鼠的气道炎症主要由淋巴细胞和嗜酸性粒细胞组成。LTC4S-Tg小鼠支气管肺泡灌洗液（BALF）中Th2细胞因子（IL-4、IL-13）和TGF-β的产生比野生型小鼠更多。同时给予博莱霉素可进一步增强LTC4S-Tg小鼠和野生型小鼠的气道炎症反应，并使TGF-β升高，其中LTC4S-Tg小鼠的气道炎症反应程度更强，提示抗原处理后的气道炎症反应可能促进和加速了博莱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的产生可能参与了气道炎症。此外，由于与野生型小鼠相比，LTC4S-Tg小鼠显示出炎症和细胞因子产生的加强，因此LTC4可能通过直接和/或间接促进Th2细胞因子和TGF-β来减轻Belomyin诱导的肺纤维化。目前正在进行组织学检查，以确认LTC4和抗原诱导的反应对博来霉素诱导的肺纤维化的影响。