|Chinese medicine Angelica sinensis suppresses radiation-induced expression of TNF-α and TGF-β1 in mice|
Authors: Cong-Hua Xie, Ming-Sheng Zhang, Yun-Feng Zhou, Guang Han, Zhen Cao, Fu-Xiang Zhou, Gong Zhang, Zhi-Guo Luo, Jian-Ping Wu, Hui Liu, Ji Chen, Wen Jie Zhang
Department of Cancer Radio-Chemotherapy, Wuhan University Zhongnan Hospital and Cancer Research Center, Wuhan, Hubei 430071, P.R. China
Radiotherapy of thoracic cancer often causes pulmonary inflammation leading to pneumonitis and fibrosis. We favor the hypothesis that cytokine-mediated multicellular interactions may result in the overexpression of proinflammatory cytokines such as TNF-α and TGF-β1, which promotes progressive radiation-induced lung injury. The root of Angelica sinensis, known as ‘Danggui’ in Chinese medicine, is widely used to treat radiation-induced pneumonitis in humans and shows clinical efficacy and low/no toxicity with an unclear mechanism. Using quantitative RT-PCR and immunohistochemistry (IHC) methods, we investigated radiation-induced lung injury in a mouse model. C57BL/6 mice were assigned to 4 groups: no treatment (NT), Angelica Sinensis treatment only (AS), X-ray irradiation only (XRT, single fraction of 12 Gy irradiation to the thoraces) and AS treatment plus XRT (AS/XRT). Mice in NT and AS groups exhibited low TNF-α and TGF-β1 mRNA levels and few positive cell counts for TNF-α (8-17 cells per field, x400 magnification) and TGF-β1 (9-31 cells per field), respectively. In XRT mice, there were increased inflammatory cells positive for TNF-α and TGF-β1 in lung tissue compared with NT mice (P<0.01). However, when XRT mice received AS treatment (AS/XRT), the number of inflammatory cells in lung tissue positive for both TNF-α and TGF-β1 was decreased compared with XRT-only mice (P<0.01) accompanied by moderately decreased mRNA levels of TNF-α and TGF-β1. We conclude that radiation induces expression of TNF-α and TGF-β1 in the inflammatory cells of irradiated lung tissue during the pneumonic phase. The predominant localization of TNF-α and TGF-β1 in inflammatory cell infiltrates suggests these cytokines' involvement in the process of radiation-induced pneumonitis. Moreover, effective down-regulation of TNF-α and TGF-β1 in irradiated lung tissue by Angelica Sinensis is, at least in part, indicative of its clinical efficacy in treating radiation-induced pneumonitis.