Study on molecular mechanisms of development of interstitial pneumonia

已有报道称，辅助性淋巴细胞参与了间质性肺炎后肺纤维化的发生。近年来，虽然有报道称白三烯C4 （LTC4）也参与肺纤维化，但其作用尚不清楚。然后，为了进一步发展间质性肺炎和肌瘤的治疗，我们分析了淋巴细胞活化和LTC4诱导的气道炎症对博莱霉素诱导的肺纤维化的影响。为此，将LTC4合成酶基因（LTC4S）转基因（Tg）小鼠和野生型小鼠分别用卵清蛋白(OVA)/明胶致敏。我们分析了抗原诱导的炎症和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OVA后LTC4S-Tg小鼠以淋巴细胞和嗜酸性粒细胞为主的气道炎症增强。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增加。在LTC4S-Tg小鼠和野生型小鼠中，同时暴露博来霉素可进一步增强ova诱导的气道炎症（TGF-β升高），且在LTC4S-Tg小鼠中程度更强。这些结果提示抗原后气道炎症可能促进和加速博莱霉素诱导的肺纤维化。虽然其机制尚不清楚，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的发生。此外，与野生型小鼠相比，LTC4S-Tg小鼠表现出炎症和细胞因子产生的增强，LTC4可能通过直接和/或间接促进Th2细胞因子和TGF-β而加重belomyin诱导的肺纤维化。目前正在进行组织学检查，以确认LTC4和抗原诱导反应对博莱霉素诱导的肺纤维化的影响。

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.