TNF-TNFR2/p75 Signaling Inhibits Early and Increases Delayed Nontargeted Effects in Bone Marrow-derived Endothelial Progenitor Cells

Sasi, Sharath P.; Song, Jin Sook; Park, Daniel; Enderling, Heiko; McDonald, J. Tyson; Gee, Hannah; Garrity, Brittany; Shtifman, Alexander; Yan, Xinhua; Walsh, Kenneth; Natarajan, Mohan; Kishore, Raj; Goukassian, David A.

doi:10.1074/jbc.m114.567743

Cited by 16 publications

(18 citation statements)

References 93 publications

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“…The activation of the TNFR signaling pathway, one of the apoptosis p53 independent pathways, has also been shown highly radiation responsive in many tissues and cells (53). Consistent with the fact that inflammatory processes are involved in the initial events triggering atherosclerotic development after radiation exposure, we observed that inflammation associated pathways (NF-kB and Toll like receptor pathways) are sensitive to proton and gamma radiation exposure in a dosage-dependent manner (54).…”

Section: Discussionsupporting

confidence: 80%

Distinct vascular genomic response of proton and gamma radiation

Emanuela

Sarantopoulou

et al. 2018

Preprint

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Purpose. The cardiovascular biology of proton radiotherapy is not well understood. We aimed to compare the genomic dose-response to proton and gamma radiation of the mouse aorta to assess whether their vascular effects may diverge. Materials and methods.We performed comparative RNA sequencing of the aorta following (4 hrs) total-body proton and gamma irradiation (0.5 -200 cGy whole body dose, 10 dose levels) of conscious mice. A trend analysis identified genes that showed a dose response.Results. While fewer genes were dose-responsive to proton than gamma radiation (29 vs. 194 genes; q-value ≤ 0.1), the magnitude of the effect was greater. Highly responsive genes were enriched for radiation response pathways (DNA damage, apoptosis, cellular stress and inflammation; p-value ≤ 0.01). Gamma, but not proton radiation induced additionally genes in vasculature specific pathways. Genes responsive to both radiation types showed almost perfectly superimposable dose-response relationships. Conclusions.Despite the activation of canonical radiation response pathways by both radiation types, we detected marked differences in the genomic response of the murine aorta. Models of cardiovascular risk based on photon radiation may not accurately predict the risk associated with proton radiation.

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Section: Discussionsupporting

confidence: 80%

Distinct vascular genomic response of proton and gamma radiation

Emanuela

Sarantopoulou

et al. 2018

Preprint

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“…that trigger inflammation and other cellular effects. [14][15][16] IL-10 has been identified as an immunosuppressive and anti-inflammatory cytokine secreted by monocytes, Th 2 cells, B cells, mast cells, dendritic and regulatory T cells, etc. [17][18][19] Upon irradiation, IL-10 expression has been found to be amplified, which affects antigen presentation capacity of APCs, resulting in inhibition of Th 1 cells activation in irradiated cells 20 resulting in immunosuppression.…”

Section: Introductionmentioning

confidence: 99%

In vitro stimulatory effect of N‐acetyl tryptophan‐glucopyranoside against gamma radiation induced immunosuppression

Malhotra

Singh

Kumar

2017

Environmental Toxicology

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Radiation-induced manifestations like free radical burst, oxidative damage and apoptosis leading to cell death. In present study, N-acetyl tryptophan glucopyranoside (NATG) was assessed for its immune-radioprotective activities using J774A.1 cells. Clonogenic cell survival, cell cycle progression and cytokines i.e. IFN-γ, TNF-α, IL-2, IL-10, IL-12, IL-13 and IL-17A expression were evaluated in irradiated and NATG pretreated cells using clonogenic formation ability, flow cytometry and ELISA assay. Results indicated that 0.25μg/ml NATG exhibited maximum radioprotection against gamma-radiation (2Gy) without intervening in cell cycle progression. NATG pretreated (-2 h) plus irradiated cells showed significant elevation in IFN-γ (∼38.2%), IL-17A (∼53.7%) and IL-12 (∼58.8%) expression as compared to only irradiated cells. Conversely, significant decrease in TNF-α (∼21.6%), IL-10 (∼31.2%), IL-2 (∼23.7%) and IL-13 expression (∼17.8%) were observed in NATG pretreated plus irradiated cells as compared to irradiated cells. Conclusively, NATG pretreatment to irradiated J774A.1 cells, stimulate Th while diminish Th cytokines that contributes to radioprotection.

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“…The mechanisms underlying RIBE have been one of the hot topics in radiation biology since 1992, when Nagasawa et al, demonstrated the phenomenon of RIBE [1]. RIBE are the consequences of intercellular communication by nature, which can be mediated through intercellular gap junctions [5], reactive oxygen species (ROS) / nitric oxide (NO) [20][21][22] and soluble signaling molecules such as cytokines [23]. For example, interleukin-6, 8, 33 and tumor growth factor β1 (TGF-β1) have been found to be one of the RIBE mediators [2,24].…”

Section: Discussionmentioning

confidence: 99%

Bystander Effects Induced by the Monolayer and Three Dimensional Cultures Exposed to Ionizing Radiation

Chen¹,

Du²

2015

J Cell Sci Ther

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Although monolayer cells culture model has played great role in the study of biological phenomena and mechanisms about bystander effect, three dimensional (3D) culture model is believed to be much more appropriate in mimicking the in vivo physiological processes. In this study, human lung bronchial epithelial cells were firstly cultured in both 3D and monolayer model, then irradiated by X-rays and high-LET carbon ions, and finally co-cultured with normal lung fibroblast cell. The bystander γH2AXfoci were found in both recipient fibroblast cells co-cultured with irradiated monolayer and 3D cells. It is of interest that significantly more bystander γH2AXfoci were induced by the monolayer cells than by the 3D cells after X-ray irradiation, while the numbers of bystander γH2AXfoci induced by both donor cells were comparative after carbon ion irradiation. Our results suggest that the magnitude of the bystander effect depended on the culture morphology and radiation quality.

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TNF-TNFR2/p75 Signaling Inhibits Early and Increases Delayed Nontargeted Effects in Bone Marrow-derived Endothelial Progenitor Cells

Cited by 16 publications

References 93 publications

Distinct vascular genomic response of proton and gamma radiation

Distinct vascular genomic response of proton and gamma radiation

In vitro stimulatory effect of N‐acetyl tryptophan‐glucopyranoside against gamma radiation induced immunosuppression

Bystander Effects Induced by the Monolayer and Three Dimensional Cultures Exposed to Ionizing Radiation

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