AUTHOR=Tian Xiaoli , Wang Feng , Luo Yuan , Ma Shijing , Zhang Nannan , Sun Yingming , You Chengcheng , Tang Guiliang , Li Shuying , Gong Yan , Xie Conghua TITLE=Protective Role of Nuclear Factor-Erythroid 2-Related Factor 2 Against Radiation-Induced Lung Injury and Inflammation JOURNAL=Frontiers in Oncology VOLUME=8 YEAR=2018 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2018.00542 DOI=10.3389/fonc.2018.00542 ISSN=2234-943X ABSTRACT=

Radiation-induced lung injury (RILI) is one of the most common and fatal complications of thoracic radiotherapy. Inflammatory cell infiltration, imbalance of inflammatory cytokines, and oxidative damage were reported to be involved during RILI pathogenesis, especially in the early phase of RILI. Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a key transcriptional regulator of antioxidative cascades, and regulates life span of mice after administration of thoracic irradiation. We investigated the effects of Nrf2 on RILI and inflammation using Nrf2-knockout, Nrf2-overexpression and wild-type mice with or without 15 Gy ionizing radiation to thorax. Our results showed that Nrf2 deficiency aggravated radiation-induced histopathological changes, macrophage and neutrophil infiltration, serum levels of pro-inflammatory cytokines (IL-6, MCP-1, IFN-γ, TNF, and IL-12p70), and the levels of peroxidation products in the mouse lung. Moreover, loss of Nrf2 reduced radiation-induced serum levels of anti-inflammatory cytokine, IL-10, and antioxidative proteins. Nrf2 overexpression significantly alleviated radiation-induced histopathological changes, macrophages and neutrophils infiltration, serum levels of pro-inflammatory cytokines, and the levels of peroxidation products in lung tissues. Nrf2 overexpression also increased the serum levels of IL-10 and antioxidative proteins. These results indicated that Nrf2 had a protective role against radiation-induced acute lung injury and inflammation, and that antioxidative therapy might be a promising treatment for RILI.