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
Published on: 01 June 2006
- Pages: 1429-1436
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.