Effect of Interferon- γ on Radiation-induced Lung Injury

γ干扰素对放射性肺损伤的影响

• 批准号: 13670968
• 负责人: TANIGAKI Toshimori
• 金额: $ 0.96万
• 依托单位: Tokai University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670968/
• 关键词: pulmonary fibrosis; radiation-induced lung injury; interferon-γ; NMR relaxation time; TGF-β1; procollagen α1(I); connective-tissue growth factor; 投与開始時期; 放射線; T_1; mRNA; TGFβ_1

Radiation-induced fibrosis (RF) is one of limiting factors in radiation therapy for thoracic malignancies and can be cured by no means. IFN-γ has been shown to inhibit collagen synthesis in vitro and in vivo including clinical idiopathic pulmonary fibrosis (IPF). We first examined effect of IFN-γ on radiation fibrosis and on TGF-β1 and connective-tissue growth factor (CTGF) mRNA levels in lung tissue that received 20 Gy in one fraction in the left hemithorax. Wistar rats were divided into 3 groups: control (C), radiation control (RC) and radiation + treatments (RT). The RT group was treated with methylprednisolone 21-acetate (2mg/kg, i.m.) 6 hr before and once a week until Week 8 and with IFN-γ (4μg/kg, s.c.) three times a week from Week 4 to 24. Experiments were performed at Week 8, 16 and 24. Fibrotic change was evaluated with histologic specimens and using NMR relaxation time (T1) of the lung tissues and there was no significant difference in them. In the mRNA levels, there was no s … More ignificant difference except for CTGF that was increased significantly in the RC group only at Week 8. These results show that IFN-γ does not attenuate RF in rat and seems to be related to the irradiation dosage, steroid and timing to begin IFN-γ administration.We then examined the effect of IFN-γ on RPF with 10 Gy without steroid. Wistar rats were divided into 5 groups: a control group (C), a radiation control group (RC), a pre-treated radiation group (Pre-RT), a group with treatment begun 1 week after radiation (1w-RT) and a group with treatment begun 2 weeks after radiation (2w-RT). The RT groups were treated with IFN-γ (4μg/kg, s.c.) three times a week. Fibrotic change was evaluated at Week 16 using T1 of lung tissues which correlates inversely with the degree of fibrosis. Irradiation shortened T1 significantly, an effect mitigated by IFN-γ, only in the Pre-RT and 1w-RT groups. We then measured TGF-β1, CTGF, and procollagen α 1(I) mRNA levels in lung tissue at Week 1 and 2 to elucidate the mechanism of the IFN effect. Irradiation increased CTGF and procollagen α 1(I) mRNA levels significantly at Week 1 and 2. IFN-γ reduced TGF-β1 and procollagen α 1(I) mRNA levels in the Pre-RT and 1w-RT groups at Week 2. These results suggest that attenuation of RPF at Week 16 as measured by T1 may be related to reduction of TGF-β1 and procollagen α 1(I) mRNA levels at Week 2 induced by IFN-γ administered up to 1 week after irradiation. Less

放射性纤维化（RF）是胸部恶性肿瘤放射治疗的限制因素之一，且无法治愈。已显示IFN-γ在体外和体内抑制胶原合成，包括临床特发性肺纤维化（IPF）。我们首先检测了IFN-γ对放射性纤维化的影响以及对左半胸一次性接受20戈伊的肺组织中TGF-β 1和结缔组织生长因子（CTGF）mRNA水平的影响。Wistar大鼠分为对照组（C组）、辐射对照组（RC组）和辐射+治疗组（RT组）。RT组给予甲基强的松龙21-醋酸酯2mg/kg，i.m.在第8周前6小时和每周一次给药，并在第8周前给予IFN-γ（4 μ g/kg，s.c.）从第4周至第24周，每周三次。在第8、16和24周进行实验。用组织学标本和肺组织的核磁共振弛豫时间（T1）评价纤维化变化，两者无显著差异。在mRNA水平上， ...更多信息 除了仅在第8周时RC组中CTGF显著增加之外，其他差异均显著。结果表明，IFN-γ对大鼠RF无明显的抑制作用，且与照射剂量、激素及开始应用IFN-γ的时间有关。将Wistar大鼠分为5组：对照组（C）、辐射对照组（RC）、辐射预处理组（Pre-RT）、辐射后1周开始处理组（1w-RT）和辐射后2周开始处理组（2w-RT）。RT组用IFN-γ（4 μ g/kg，s.c.）一周三次在第16周使用与纤维化程度呈负相关的肺组织T1评价纤维化变化。仅在Pre-RT和1w-RT组中，照射显著缩短了T1，IFN-γ减轻了这种效应。然后，我们在第1周和第2周测量肺组织中TGF-β 1、CTGF和前胶原α 1（I）mRNA水平，以阐明IFN效应的机制。照射在第1周和第2周显著增加CTGF和前胶原α 1（I）mRNA水平。在第2周，IFN-γ降低了Pre-RT和1w-RT组的TGF-β 1和前胶原α 1（I）mRNA水平。这些结果表明，在第16周通过T1测量的RPF衰减可能与在照射后1周给予IFN-γ诱导的第2周TGF-β 1和前胶原α 1（I）mRNA水平降低有关。少

项目成果

Tanigaki T, Tsuji C, Shioya S: "Effect of Interferon-γ on Radiation-induced Fibrosis in Rat Lung"Am J Respir Crit Care Med. 163. A3 (2001)

Tanigaki T、Tsuji C、Shioya S：“干扰素 γ 对辐射诱导的大鼠肺纤维化的影响”Am J Respir Crit Care Med 163。A3 (2001)