title: Chinese medicine Angelica sinensis suppresses radiation-induced expression of TNF-alpha and TGF-beta1 in mice.
abstract: 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-alpha and TGF-beta1, 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-alpha and TGF-beta1 mRNA levels and few positive cell counts for TNF-alpha (8-17 cells per field, x400 magnification) and TGF-beta1 (9-31 cells per field), respectively. In XRT mice, there were increased inflammatory cells positive for TNF-alpha and TGF-beta1 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-alpha and TGF-beta1 was decreased compared with XRT-only mice (P<0.01) accompanied by moderately decreased mRNA levels of TNF-alpha and TGF-beta1. We conclude that radiation induces expression of TNF-alpha and TGF-beta1 in the inflammatory cells of irradiated lung tissue during the pneumonic phase. The predominant localization of TNF-alpha and TGF-beta1 in inflammatory cell infiltrates suggests these cytokines' involvement in the process of radiation-induced pneumonitis. Moreover, effective down-regulation of TNF-alpha and TGF-beta1 in irradiated lung tissue by Angelica Sinensis is, at least in part, indicative of its clinical efficacy in treating radiation-induced pneumonitis.
authors: Department of Cancer Radio-Chemotherapy, Wuhan University Zhongnan Hospital and Cancer Research Center, Wuhan, Hubei 430071, P.R. China.
authors: Cong-Hua
authors: CH
authors: Xie
authors: Ming-Sheng
authors: MS
authors: Zhang
authors: Yun-Feng
authors: YF
authors: Zhou
authors: Guang
authors: G
authors: Han
authors: Zhen
authors: Z
authors: Cao
authors: Fu-Xiang
authors: FX
authors: Zhou
authors: Gong
authors: G
authors: Zhang
authors: Zhi-Guo
authors: ZG
authors: Luo
authors: Jian-Ping
authors: JP
authors: Wu
authors: Hui
authors: H
authors: Liu
authors: Ji
authors: J
authors: Chen
authors: Wen Jie
authors: WJ
authors: Zhang