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Genistein Alleviates Radiation-Induced Pneumonitis by Depressing Ape1/Ref-1 Expression to Down-regulate Inflammatory Cytokines

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Abstract

The aim of the study was to investigate the role of genistein in alleviating radiation-induced pneumonitis (RIP) through down-regulating levels of the inflammatory cytokines by inhibiting the expression of apurinic/apyrimidinic endonuclease 1/redox factor-1 (Ape1/Ref-1). Fifty female C57BL/6J mice (8 weeks old) were randomly divided into a control group, a pure irradiation (IR) group and a genistein + IR group. At the four time points after IR, hematoxylin, and Masson’s trichrome stainings were used to examine the pathological changes and collagen fiber deposition. Flow cytometry was used to detect reactive oxygen system (ROS) changes, EMSA was used to estimate the nuclear factor kappa B (NF-κB) transcriptional activities and an ELISA assay was used to measure the levels of TGF-β1, IL-1β, TNF-α, and IL-6 in the serum and bronchoalveolar lavage fluid (BALF) 2 weeks after IR. The pathological detection results showed acute inflammatory/fibrinoid exudation of the thoracic tissue after IR, which was significantly alleviated with genistein. The IR-induced an APE1 protein expression increase and NF-κB was effectively suppressed by genistein (P < 0.05). The induction of the inflammatory cytokines TGF-β1, IL-1β, TNF-α, and IL-6 by IR were in turn inhibited in the serum and BALF of the genistein-pretreated mice (P < 0.05). In addition, the ROS production was significantly boosted in the A549 cells after IR, which could be down-regulated by the pretreatment of genistein. The results demonstrate that genistein alleviates RIP by attenuating the inflammatory response in the initiation of RIP. A possible target of genistein is the Ape1/ref-1, which regulates key inflammatory cytokines by activating the NF-κB.

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Acknowledgments:

We thank Ms. Yu-Xin Yang, and Ms. Ling Liao for their kind and excellent technical assistance. This study was supported by grants from the National Natural Science Foundation of China (No. 30970865, 81272499, 81101783), National Natural Science Foundation of Chongqing (CSTC2010BB5030) and Initial Fund for Returnees of Third Military Medical University (2009XHG17) to Prof. Zhen-Zhou Yang and Military Twelfth Five Key Projects (BWS11J038) to Guo-Dong Liu.

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Authors and Affiliations

  1. Cancer Center, Institute of Surgery Research, Daping Hospital, Third Military Medical University, 10 Changjiang Zhilu, Daping Yuzhong District, Chongqing, 400042, People’s Republic of China

    Lei Xia, Jian-Wu Zhu, Meng-Xia Li, Wei Luo, Juan Li, Qian Zhou, Xue-Qin Yang, Jin-Lu Shan, Ge Wang, Dong Wang & Zhen-Zhou Yang

  2. Eighth Department, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, 400042, People’s Republic of China

    Guo-Dong Liu

  3. Department of Anesthesiology, General Hospital of Chengdu Military Command, Chengdu, Sichuan, 610083, People’s Republic of China

    Shan Ou

  4. Department of Respiration, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, 400042, People’s Republic of China

    Yong He

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  1. Guo-Dong Liu
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  2. Lei Xia
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  13. Dong Wang
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  14. Zhen-Zhou Yang
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Correspondence to Dong Wang or Zhen-Zhou Yang.

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Guo-Dong Liu and Lei Xia contributed equally to this work.

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Liu, GD., Xia, L., Zhu, JW. et al. Genistein Alleviates Radiation-Induced Pneumonitis by Depressing Ape1/Ref-1 Expression to Down-regulate Inflammatory Cytokines. Cell Biochem Biophys 69, 725–733 (2014). https://doi.org/10.1007/s12013-014-9859-x

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  • DOI: https://doi.org/10.1007/s12013-014-9859-x

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