Radiation triggering immune response and inflammation

Hekim, Nezih; Çetin, Zafer; Nikitaki, Zacharenia; Çört, Ayşegül; Saygılı, Eyüp İlker

doi:10.1016/j.canlet.2015.04.016

Cited by 87 publications

(65 citation statements)

References 80 publications

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“…This region of neurogenesis is particularly sensitive to ionising radiation [79], as mitotic cells are radiosensitive at stages of the cell cycle between the G2 and M phase [80], [81], [82], [83]. Doses of ionising radiation above 1 Gy can influence neural progenitor cell survival in the hippocampus by significantly reducing the number of newly differentiated cells, increasing DNA damage (

γ

-H2AX nuclear foci), promoting cell-cycle arrest, and inducing oxidative/nitrosative stress, which ultimately implicates the functionality of the hippocampus manifesting as cognitive impairment [84], [85], [86], [87], [88].…”

Section: The Impact Of High Dose Ionising Radiation On the Cnsmentioning

confidence: 99%

The impact of high and low dose ionising radiation on the central nervous system

et al. 2016

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Responses of the central nervous system (CNS) to stressors and injuries, such as ionising radiation, are modulated by the concomitant responses of the brains innate immune effector cells, microglia. Exposure to high doses of ionising radiation in brain tissue leads to the expression and release of biochemical mediators of ‘neuroinflammation’, such as pro-inflammatory cytokines and reactive oxygen species (ROS), leading to tissue destruction. Contrastingly, low dose ionising radiation may reduce vulnerability to subsequent exposure of ionising radiation, largely through the stimulation of adaptive responses, such as antioxidant defences. These disparate responses may be reflective of non-linear differential microglial activation at low and high doses, manifesting as an anti-inflammatory or pro-inflammatory functional state. Biomarkers of pathology in the brain, such as the mitochondrial Translocator Protein 18 kDa (TSPO), have facilitated in vivo characterisation of microglial activation and ‘neuroinflammation’ in many pathological states of the CNS, though the exact function of TSPO in these responses remains elusive. Based on the known responsiveness of TSPO expression to a wide range of noxious stimuli, we discuss TSPO as a potential biomarker of radiation-induced effects.

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Section: The Impact Of High Dose Ionising Radiation On the Cnsmentioning

confidence: 99%

The impact of high and low dose ionising radiation on the central nervous system

et al. 2016

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“…A detailed overview of existing literature data about mediators of local and systemic bystander effects as well as mechanisms how RIBE develop has been recently published (5). The in vivo studies related to immune responses elicited by direct radiation and bystander signals have been recently rewieved by Hekim et al also, listing many important pathways mediating T-cell activation (or suppression), antigen-presenting cell, and natural killer (NK) cell activation (15). …”

Section: Introductionmentioning

confidence: 99%

Extracellular Vesicles Mediate Radiation-Induced Systemic Bystander Signals in the Bone Marrow and Spleen

et al. 2017

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Radiation-induced bystander effects refer to the induction of biological changes in cells not directly hit by radiation implying that the number of cells affected by radiation is larger than the actual number of irradiated cells. Recent in vitro studies suggest the role of extracellular vesicles (EVs) in mediating radiation-induced bystander signals, but in vivo investigations are still lacking. Here, we report an in vivo study investigating the role of EVs in mediating radiation effects. C57BL/6 mice were total-body irradiated with X-rays (0.1, 0.25, 2 Gy), and 24 h later, EVs were isolated from the bone marrow (BM) and were intravenously injected into unirradiated (so-called bystander) animals. EV-induced systemic effects were compared to radiation effects in the directly irradiated animals. Similar to direct radiation, EVs from irradiated mice induced complex DNA damage in EV-recipient animals, manifested in an increased level of chromosomal aberrations and the activation of the DNA damage response. However, while DNA damage after direct irradiation increased with the dose, EV-induced effects peaked at lower doses. A significantly reduced hematopoietic stem cell pool in the BM as well as CD4+ and CD8+ lymphocyte pool in the spleen was detected in mice injected with EVs isolated from animals irradiated with 2 Gy. These EV-induced alterations were comparable to changes present in the directly irradiated mice. The pool of TLR4-expressing dendritic cells was different in the directly irradiated mice, where it increased after 2 Gy and in the EV-recipient animals, where it strongly decreased in a dose-independent manner. A panel of eight differentially expressed microRNAs (miRNA) was identified in the EVs originating from both low- and high-dose-irradiated mice, with a predicted involvement in pathways related to DNA damage repair, hematopoietic, and immune system regulation, suggesting a direct involvement of these pathways in mediating radiation-induced systemic effects. In conclusion, we proved the role of EVs in transmitting certain radiation effects, identified miRNAs carried by EVs potentially responsible for these effects, and showed that the pattern of changes was often different in the directly irradiated and EV-recipient bystander mice, suggesting different mechanisms.

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“…However, increases in polyunsaturated fatty acids (PUFAs) are consistent with increased apoptosis and a proinflammatory phenotype associated with radiation responses. 32–34 Indicative of this is the increased circulating levels of ubiquinone Q2, a precursor of ubiquinone Q10 synthesis. Ubiquinone Q10 plays a significant role in ATP production in mitochondria through the electron transport chain and possible reduction in oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

A Serum Small Molecule Biosignature of Radiation Exposure from Total Body Irradiated Patients

Laiakis¹,

Pannkuk²,

Chauthe³

et al. 2017

J. Proteome Res.

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The potential for radiological accidents and nuclear terrorism has increased the need for the development of new rapid biodosimetry methods. In addition, in a clinical setting the issue of an individual’s radiosensitivity should be taken into consideration during radiotherapy. We utilized metabolomics and lipidomics to investigate changes of metabolites in serum samples following exposure to total body ionizing radiation in humans. Serum was collected prior to irradiation, at 3–8 h after a single dose of 1.25–2 Gy, and at 24 h with a total delivered dose of 2–3.75 Gy. Metabolomics revealed perturbations in glycerophosphocholine, phenylalanine, ubiquinone Q2, and oxalic acid. Alterations were observed in circulating levels of lipids from monoacylglycerol, triacylglycerol, phosphatidylcholine, and phosphatidylglycerol lipid classes. Polyunsaturated fatty acids were some of the most dysregulated lipids, with increased levels linked to proinflammatory processes. A targeted metabolomics approach for eicosanoids was also employed. The results showed a rapid response for proinflammatory eicosanoids, with a dampening of the signal at the later time point. Sex differences were observed in the markers from the untargeted approach but not the targeted method. The ability to identify and quantify small molecules in blood can therefore be utilized to monitor radiation exposure in human populations.

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Radiation triggering immune response and inflammation

Cited by 87 publications

References 80 publications

The impact of high and low dose ionising radiation on the central nervous system

The impact of high and low dose ionising radiation on the central nervous system

Extracellular Vesicles Mediate Radiation-Induced Systemic Bystander Signals in the Bone Marrow and Spleen

A Serum Small Molecule Biosignature of Radiation Exposure from Total Body Irradiated Patients

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