Baoqing Chen1, Feifei Na2, Hui Yang1, Rui Li3, Mengqian Li3, Xiaowen Sun3, Binbin Hu3, Guodong Huang3, Jie Lan3, He Xu3, Ruizhan Tong3, Xianming Mo4, Jianxin Xue5, You Lu6. 1. Department of Thoracic Oncology, Cancer Center, West China Hospital, Sichuan University, 37 Guoxue Lane, Chengdu, Sichuan, 610041, China; Huaxi Student Society of Oncology Research, West China School of Medicine, Sichuan University, 37 Guoxue Lane, Chengdu, Sichuan, 610041, China. 2. Department of Thoracic Oncology, Cancer Center, West China Hospital, Sichuan University, 37 Guoxue Lane, Chengdu, Sichuan, 610041, China; Huaxi Student Society of Oncology Research, West China School of Medicine, Sichuan University, 37 Guoxue Lane, Chengdu, Sichuan, 610041, China; Department of Thoracic Cancer, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, West China School of Medicine, Sichuan University and Collaborative Innovation Center,37 Guoxue Lane, Chengdu, Sichuan, 610041, China. 3. Department of Thoracic Oncology, Cancer Center, West China Hospital, Sichuan University, 37 Guoxue Lane, Chengdu, Sichuan, 610041, China. 4. Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China. 5. Department of Thoracic Oncology, Cancer Center, West China Hospital, Sichuan University, 37 Guoxue Lane, Chengdu, Sichuan, 610041, China. Electronic address: xuejx@scu.edu.cn. 6. Department of Thoracic Oncology, Cancer Center, West China Hospital, Sichuan University, 37 Guoxue Lane, Chengdu, Sichuan, 610041, China; Huaxi Student Society of Oncology Research, West China School of Medicine, Sichuan University, 37 Guoxue Lane, Chengdu, Sichuan, 610041, China. Electronic address: radyoulu@hotmail.com.
Abstract
OBJECTIVE: Radiation-induced lung injury (RILI) is a common complication of thoracic cancer radiation therapy. Ethyl pyruvate (EP) was reported to have an ameliorating effect on a variety of systemic inflammation reactions, including acute lung injury. However, the protective effect of EP on RILI has not been explored. MATERIALS/ METHODS: RILI was induced by a single thoracic irradiation of 16Gy X-rays in C57BL/6 mice. Mice were divided into four groups: control, radiation, 100mg/kg EP, and 200mg/kg dexamethasone. Inflammation and fibrosis grade of lung tissue were scored by H&E and Masson's trichrome staining. Cytokines include IL-1β, IL-6, TNF-α, GM-CSF, M-CSF, TGF-β1, and HMGB1 were measured after irradiation. Colony formation assay was performed to determine the protective effect of EP in RAW264.7 and HBE cells. The effect of EP on HMGB1 was also explored in vitro. RESULT: The cytoplasm of bronchial epithelium cells in mice was positive-stained of HMGB1 accompanying with an increase of HMGB1, IL-6, IL-1β, GM-CSF, M-CSF, TNF-α, and TGF-β1 after irradiation. EP prescription significantly reduced pulmonary inflammation infiltration of RILI, along with a decrease of HMGB1, IL-6, IL-1β, and GM-CSF at 4 weeks after irradiation. Furthermore, EP decreased radiation-induced collagen deposition at 20 weeks after irradiation. Pro-fibrotic cytokines including TGF-β1 and HMGB1 in irradiated lung tissue and plasma obviously decreased in EP administration group in the later stage. In vitro, EP administration protected HBE cells from radiation injury. EP also rescued radiation-induced release but not translocation of HMGB1 in RAW264.7 and HBE cells. CONCLUSION: EP treatment ameliorates RILI, including radiation-induced fibrosis in mice. The inhibition of production and release of pro-inflammatory or fibrotic cytokines, especially HMGB1, may partly attribute to its attenuating RILI effect.
OBJECTIVE: Radiation-induced lung injury (RILI) is a common complication of thoracic cancer radiation therapy. Ethyl pyruvate (EP) was reported to have an ameliorating effect on a variety of systemic inflammation reactions, including acute lung injury. However, the protective effect of EP on RILI has not been explored. MATERIALS/ METHODS: RILI was induced by a single thoracic irradiation of 16Gy X-rays in C57BL/6 mice. Mice were divided into four groups: control, radiation, 100mg/kg EP, and 200mg/kg dexamethasone. Inflammation and fibrosis grade of lung tissue were scored by H&E and Masson's trichrome staining. Cytokines include IL-1β, IL-6, TNF-α, GM-CSF, M-CSF, TGF-β1, and HMGB1 were measured after irradiation. Colony formation assay was performed to determine the protective effect of EP in RAW264.7 and HBE cells. The effect of EP on HMGB1 was also explored in vitro. RESULT: The cytoplasm of bronchial epithelium cells in mice was positive-stained of HMGB1 accompanying with an increase of HMGB1, IL-6, IL-1β, GM-CSF, M-CSF, TNF-α, and TGF-β1 after irradiation. EP prescription significantly reduced pulmonary inflammation infiltration of RILI, along with a decrease of HMGB1, IL-6, IL-1β, and GM-CSF at 4 weeks after irradiation. Furthermore, EP decreased radiation-induced collagen deposition at 20 weeks after irradiation. Pro-fibrotic cytokines including TGF-β1 and HMGB1 in irradiated lung tissue and plasma obviously decreased in EP administration group in the later stage. In vitro, EP administration protected HBE cells from radiation injury. EP also rescued radiation-induced release but not translocation of HMGB1 in RAW264.7 and HBE cells. CONCLUSION:EP treatment ameliorates RILI, including radiation-induced fibrosis in mice. The inhibition of production and release of pro-inflammatory or fibrotic cytokines, especially HMGB1, may partly attribute to its attenuating RILI effect.
Authors: Guanmin Meng; Melinda Wuest; Xiaoyun Tang; Jennifer Dufour; Todd P W McMullen; Frank Wuest; David Murray; David N Brindley Journal: Cancers (Basel) Date: 2020-04-18 Impact factor: 6.639