Role of PLC-PIP2 and cAMP-PKA Signal Pathways in Radiation-induced Immune-suppressing Effect

作     者：DONG Juan Cong CHENG Guang Hui SHAN Yu Xing WU Ning SHAO Ming Long LI Peng Wu JIN Shun Zi 

作者机构：Ministry of Health Key Laboratory of RadiobiologyJilin University Department of Radiation OncologyChina-Japan Union Hospital of Jilin University Department of OrthopedicsFirst Hospital of Jilin University 

出 版 物：《Biomedical and Environmental Sciences》 (生物医学与环境科学（英文版）)

年 卷 期：2014年第27卷第1期

页      面：27-34页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by grants from the National Natural Science Foundation of China(No.30870584,No.81201737) the Doctoral Program Foundation of Institutions of Higher Education of China(No.20120061110063) 

主　　题：Ionizing radiation Neuropilin-1 (Nrpl) Regulatory T cells Signal molecule 

摘      要：Objective The purpose of the present study was to observe the changes in CD4＋CD25＋Nrpl＋Treg cells after irradiation with different doses and explore the possible molecular mechanisms involved. Methods ICR mice and mouse lymphoma cell line （EL-4 cells） was used. The expressions of CD4, CD25, Nrpl, calcineurin and PKC-α were detected by flow cytometry. The expressions of TGF-131, IL-10, PKA and cAMP were estimated with ELISA. Results At 12 h after irradiation, the expression of Nrpl increased significantly in 4.0 Gy group, compared with sham-irradiation group （P〈0.05） in the spleen and thymus, respectively, when ICR mice received whole-body irradiation （WBI）. Meanwhile the synthesis of Interleukin 10 （IL-20） and transforming growth factor-β1 （TGF-β1） increased significantly after high dose irradiation （HDR） （〉 or = 1.0 Gy）. In addition, the expression of cAMP and PKA protein increased, while PKC-α, calcineurin decreased at 12h in thymus cells after 4.0 Gy X-irradiation. While TGF-β1 was clearly inhibited when the PLC-PIP2 signal pathway was stimulated or the cAMP-PKA signal pathway was blocked after 4.0 Gy X-irradiation, this did not limit the up-regulation of CD4＋CD25＋Nrpl＋Treg cells after ionizing radiation. Conclusion These results indicated that HDR might induce CD4＋CD25＋Nrpl＋Treg cells production and stimulate TGF-β1 secretion by regulating signal molecules in mice.