title: Role of PLC-PIP2 and cAMP-PKA signal pathways in radiation-induced immune-suppressing effect.
abstract: OBJECTIVE
  The 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.
  
  
  METHODS
  ICR 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.
  
  
  RESULTS
  At 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.
  
  
  CONCLUSIONS
  These results indicated that HDR might induce CD4+CD25+Nrp1+Treg cells production and stimulate TGF-β1 secretion by regulating signal molecules in mice.
authors.affiliation: Ministry of Health Key Laboratory of Radiobiology, Jilin University, Changchun 130021, Jilin, China.
authors.forename: Juan Cong
authors.initials: JC
authors.lastname: Dong
authors.affiliation: Department of Radiation Oncology, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin, China.
authors.forename: Guang Hui
authors.initials: GH
authors.lastname: Cheng
authors.affiliation: Department of Orthopedics, First Hospital of Jilin University, Changchun 130021, Jilin, China.
authors.forename: Yu Xing
authors.initials: YX
authors.lastname: Shan
authors.affiliation: Department of Radiation Oncology, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Wu
authors.affiliation: Ministry of Health Key Laboratory of Radiobiology, Jilin University, Changchun 130021, Jilin, China.
authors.forename: Ming Long
authors.initials: ML
authors.lastname: Shao
authors.affiliation: Ministry of Health Key Laboratory of Radiobiology, Jilin University, Changchun 130021, Jilin, China.
authors.forename: Peng Wu
authors.initials: PW
authors.lastname: Li
authors.affiliation: Ministry of Health Key Laboratory of Radiobiology, Jilin University, Changchun 130021, Jilin, China.
authors.forename: Shun Zi
authors.initials: SZ
authors.lastname: Jin
mesh_terms: D000818:Animals; D019703:Calcineurin / Q000235:genetics / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005786:Gene Expression Regulation / Q000528:radiation effects; D007165:Immunosuppression Therapy; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000502:physiology; D008297:Male; D051379:Mice; D039942:Neuropilin-1 / Q000235:genetics / Q000378:metabolism; D054801:Phosphoinositide Phospholipase C / Q000235:genetics / Q000378:metabolism*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D014916:Whole-Body Irradiation / Q000009:adverse effects*
chemical_list: C556062:IL10 protein, mouse; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D039942:Neuropilin-1; D000242:Cyclic AMP; D011494:Protein Kinases; D019703:Calcineurin; D054801:Phosphoinositide Phospholipase C
keywords: Ionizing radiation; Neuropilin-1 (Nrp1); Regulatory T cells; Signal molecule