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Int J Mol Sci. 2018 Nov 21;19(11). pii: E3689. doi: 10.3390/ijms19113689.

Synergistic Effects of Weightlessness, Isoproterenol, and Radiation on DNA Damage Response and Cytokine Production in Immune Cells.

Author information

1
National Aeronautics and Space Administration (NASA), Johnson Space Center Houston, Houston, TX 77058, USA. maria.moreno-villanueva@uni-konstanz.de.
2
Molecular Toxicology Group, Department of Biology, Box 628, University of Konstanz, 78457 Konstanz, Germany. maria.moreno-villanueva@uni-konstanz.de.
3
National Aeronautics and Space Administration (NASA), Johnson Space Center Houston, Houston, TX 77058, USA. alan.h.feiveson@nasa.gov.
4
KBRwyle, 2400 NASA Parkway, Houston, TX 77058, USA. stephanie.s.krieger@nasa.gov.
5
Department of Biomedical Engineering, University of Minnesota, 312 Church Street SE, Minneapolis, MN 55455, USA. kovac149@umn.edu.
6
Molecular Toxicology Group, Department of Biology, Box 628, University of Konstanz, 78457 Konstanz, Germany. gudrun.vonscheven@uni-konstanz.de.
7
Molecular Toxicology Group, Department of Biology, Box 628, University of Konstanz, 78457 Konstanz, Germany. alexander.buerkle@uni-konstanz.de.
8
National Aeronautics and Space Administration (NASA), Johnson Space Center Houston, Houston, TX 77058, USA. brian.crucian-1@nasa.gov.
9
National Aeronautics and Space Administration (NASA), Johnson Space Center Houston, Houston, TX 77058, USA. honglu.wu-1@nasa.gov.

Abstract

The implementation of rotating-wall vessels (RWVs) for studying the effect of lack of gravity has attracted attention, especially in the fields of stem cells, tissue regeneration, and cancer research. Immune cells incubated in RWVs exhibit several features of immunosuppression including impaired leukocyte proliferation, cytokine responses, and antibody production. Interestingly, stress hormones influence cellular immune pathways affected by microgravity, such as cell proliferation, apoptosis, DNA repair, and T cell activation. These pathways are crucial defense mechanisms that protect the cell from toxins, pathogens, and radiation. Despite the importance of the adrenergic receptor in regulating the immune system, the effect of microgravity on the adrenergic system has been poorly studied. Thus, we elected to investigate the synergistic effects of isoproterenol (a sympathomimetic drug), radiation, and microgravity in nonstimulated immune cells. Peripheral blood mononuclear cells were treated with the sympathomimetic drug isoproterenol, exposed to 0.8 or 2 Gy γ-radiation, and incubated in RWVs. Mixed model regression analyses showed significant synergistic effects on the expression of the β2-adrenergic receptor gene (ADRB2). Radiation alone increased ADRB2 expression, and cells incubated in microgravity had more DNA strand breaks than cells incubated in normal gravity. We observed radiation-induced cytokine production only in microgravity. Prior treatment with isoproterenol clearly prevents most of the microgravity-mediated effects. RWVs may be a useful tool to provide insight into novel regulatory pathways, providing benefit not only to astronauts but also to patients suffering from immune disorders or undergoing radiotherapy.

KEYWORDS:

DNA damage response; adrenergic receptor; cytokines; radiation; simulated microgravity

PMID:
30469384
PMCID:
PMC6275019
DOI:
10.3390/ijms19113689
[Indexed for MEDLINE]
Free PMC Article

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