机构:[1]Department of Radiotherapy, Lanzhou General Hospital of PLA, Lanzhou, China[2]Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai, China[3]Department of Thoracic Surgery, Tongren Hospital, Shanghai Jiao Tong University of Medicine Shanghai, China
Pulmonary fibrosis is a serious adverse effect of radiotherapy for thoracic tumor, which is believed to be a process that is tightly regulated by the phenotype of the developing Th response after radiation. Here, we will investigate whether CpG-oligodeoxynucleotides (ODN) prevent radiation-induced pulmonary fibrosis by shifting the imbalance of Th1 and Th2 response and summarizes the possible mechanism. In this study, female C57BL/6 mice were chosen to preform pulmonary fibrosis model, the whole-thorax of mice was exposed to a single radiation dose of 15 Gy. When irradiated mice were administrated with CpG-ODN, forming of pulmonary fibrosis was significantly prevented. Th2-related cytokines (IL-4 and IL-13) expression decreased, Th1 related-cytokine (IFN-gamma and IL-12) expression increased. Alveolar macrophage accumulation was reduced in irradiated tissue. Profibrotic cytokine TGF-beta 1 expression stayed at lower level. In TGF-beta 1-Smad-dependent pathways, TGF-beta 1, T beta R and phosphor-Smad 2/3 were down regulated, and Smad 7 was up regulated. These suggested that CpG-ODN prevented pulmonary fibrosis after radiation. The mechanism might be associated with reduction of alveolar macrophages accumulation and profibrogenic cytokines secretion TGF-beta 1 through stimulating the combination of Th1-promoting and Th2-limiting responses after radiation, and finally inhibited the fibrosis-related downstream TGF-beta 1-Smad-dependent pathway.
基金:
National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81501623, 81472911]; Shanghai Municipal and Technology Commission Medical Guide Project [124119b1900]
第一作者机构:[1]Department of Radiotherapy, Lanzhou General Hospital of PLA, Lanzhou, China[*2]Department of radiotherapy, Lanzhou General Hospital of PLA, Lanzhou, 730050, China.
共同第一作者:
通讯作者:
通讯机构:[1]Department of Radiotherapy, Lanzhou General Hospital of PLA, Lanzhou, China[2]Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai, China[3]Department of Thoracic Surgery, Tongren Hospital, Shanghai Jiao Tong University of Medicine Shanghai, China[*1]Section of Radiation Medicine, Department of Naval Medicine, Second Military Medical University, Shanghai, 200433, China.[*2]Department of radiotherapy, Lanzhou General Hospital of PLA, Lanzhou, 730050, China.
推荐引用方式(GB/T 7714):
Zhang Chao,Zhao Hainan,Li Bai-Long,et al.CpG-oligodeoxynucleotides may be effective for preventing ionizing radiation induced pulmonary fibrosis[J].TOXICOLOGY LETTERS.2018,292:181-189.doi:10.1016/j.toxlet.2018.04.009.
APA:
Zhang, Chao,Zhao, Hainan,Li, Bai-Long,Fu-Gao,Liu, Hu...&Zheng, Min.(2018).CpG-oligodeoxynucleotides may be effective for preventing ionizing radiation induced pulmonary fibrosis.TOXICOLOGY LETTERS,292,
MLA:
Zhang, Chao,et al."CpG-oligodeoxynucleotides may be effective for preventing ionizing radiation induced pulmonary fibrosis".TOXICOLOGY LETTERS 292.(2018):181-189