Role of PLC-PIP2 and cAMP-PKA signal pathways in radiation-induced immune-suppressing effect.

Juan Cong Dong; Guang Hui Cheng; Yu Xing Shan; Ning WU; Ming Long Shao; Peng Wu LI; Shun Zi Jin

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Role of PLC-PIP2 and cAMP-PKA signal pathways in radiation-induced immune-suppressing effect.

Author: Juan Cong DONG ¹ ; Guang Hui CHENG ² ; Yu Xing SHAN ³ ; Ning WU ² ; Ming Long SHAO ¹ ; Peng Wu LI ¹ ; Shun Zi JIN ¹
Author Information

1. Ministry of Health Key Laboratory of Radiobiology, Jilin University, Changchun 130021, Jilin, China.
2. Department of Radiation Oncology, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin, China.
3. Department of Orthopedics, First Hospital of Jilin University, Changchun 130021, Jilin, China.
Publication Type:Journal Article
Keywords: Ionizing radiation; Neuropilin-1 (Nrp1); Regulatory T cells; Signal molecule
MeSH: Animals; Calcineurin; genetics; metabolism; Cyclic AMP; metabolism; Dose-Response Relationship, Radiation; Female; Gene Expression Regulation; radiation effects; Immunosuppression; Interleukin-10; genetics; metabolism; Lymphocyte Subsets; physiology; Male; Mice; Neuropilin-1; genetics; metabolism; Phosphoinositide Phospholipase C; genetics; metabolism; Protein Kinases; genetics; metabolism; Signal Transduction; Transforming Growth Factor beta; genetics; metabolism; Whole-Body Irradiation; adverse effects
From: Biomedical and Environmental Sciences 2014;27(1):27-34
CountryChina
Language:English
Abstract:
OBJECTIVEThe purpose of the present study was to observe the changes in CD4+CD25+Nrp1+Treg cells after irradiation with different doses and explore the possible molecular mechanisms involved.
METHODSICR mice and mouse lymphoma cell line (EL-4 cells) was used. The expressions of CD4, CD25, Nrp1, calcineurin and PKC-α were detected by flow cytometry. The expressions of TGF-β1, IL-10, PKA and cAMP were estimated with ELISA.
RESULTSAt 12 h after irradiation, the expression of Nrp1 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-10) 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+Nrp1+Treg cells after ionizing radiation.
CONCLUSIONThese results indicated that HDR might induce CD4+CD25+Nrp1+Treg cells production and stimulate TGF-β1 secretion by regulating signal molecules in mice.