title: Low-dose gamma-rays and simulated solar particle event protons modify splenocyte gene and cytokine expression patterns.
abstract: The goal was to investigate the T helper (Th) response in splenocytes of mice exposed to low-dose/low-dose-rate (LDR) γ-rays, simulated solar particle event protons (sSPE), or combination of both. C57BL/6 mice were exposed to LDR γ-radiation ((57)Co) to a total dose of 0.05 Gray (Gy) at 0.024 cGy/h, either with or without subsequent exposure to 2 Gy sSPE protons. Expression of genes related to Th cells was evaluated immediately after exposure (day 0). On day 21, intra- and extracellular cytokine production was assessed after activation with anti-CD3 monoclonal antibodies (mAb) or phorbol 12-myristate 13-acetate/ionophore (PMA/I). Five genes were significantly modulated on day 0 in one or more of the irradiated groups compared to controls (p < 0.05): Ccl11, Ccr5, Cd80, Inha, and Il9. On day 21, numbers of cells positive for interferon-γ were high in the LDR + sSPE group versus 0 Gy and LDR γ-rays (p < 0.05), but there was no difference in IL-2 and TNF-α. Levels of secreted cytokines after anti-CD3 mAb activation were high for 5 (MIP-1α, GM-CSF, IFN-γ, TNF-α, IL-13) and low for 2 (IL-7, IL-9) in all irradiated groups. Priming with LDR photons had a significant effect on IFN-γ and IL-17 compared to sSPE protons alone; IL-2 was low only in the LDR + sSPE group. The cytokine patterns after anti-PMA/I activation were different compared to anti-CD3 mAb and with fewer differences among groups. The data show that total-body exposure to space-relevant radiation has profound effects on Th cell status and that priming with LDR γ-rays can in some cases modulate the response to sSPE.
authors.affiliation: Department of Radiation Medicine, Division of Biochemistry and Microbiology, Loma Linda University & Medical Center Loma Linda, CA 92354, USA.
authors.forename: Asma
authors.initials: A
authors.lastname: Rizvi
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Pecaut
authors.forename: Daila S
authors.initials: DS
authors.lastname: Gridley
mesh_terms: D000818:Animals; D003359:Cosmic Radiation / Q000009:adverse effects; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005720:Gamma Rays / Q000009:adverse effects*; D015870:Gene Expression / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018561:Space Simulation; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects
chemical_list: D016207:Cytokines