Time‐ and dose‐dependent changes of intracellular cytokine and cytokine receptor profile of Ewing tumour subpopulations under the influence of ionizing radiation

Könemann, Stefan; Bölling, Tobias; Malath, J.; Kolkmeyer, Astrid; Janke, Kirsten; Riesenbeck, D.; Hesselmann, Stefan; Diallo, Raihanatou; Vormoor, Josef; Willich, Normann; Schuck, Andreas

doi:10.1080/09553000310001626126

Cited by 9 publications

(3 citation statements)

References 42 publications

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“…45 More recently, IR induced time-and dose-dependent increase in the expression of intracellular IL-1α was demonstrated. 46 Consistently, a number of studies identified the key role of IL-1α in induced radioprotection. 47 IL-1α has been demonstrated to stimulate NFκB activation through 1R-AcP that recruit IRAK1, 2/Traf6/MyD88 complex and activate NIK which in turn activate IKK1.…”

Section: Discussionmentioning

confidence: 80%

NFκB activity and transcriptional responses in human breast adenocarcinoma cells after single and fractionated irradiation

Madhusoodhanan

Natarajan²,

Veeraraghavan

et al. 2009

Cancer Biology & Therapy

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Radiotherapy is considered mandatory for breast cancer patients undergoing conservative surgery and for women at high risk of recurrence. However, relapse due to radio-resistance affects the success of radiotherapy. Ascertaining the fractionated radiation (FIR) modulated molecular targets is important to make tumors more susceptible to molecular targeted therapy. Accordingly, we investigated the (i) expression of 84 genes representing six functional pathways; (ii) NFkappaB DNA binding activity and; (iii) expression of radio-responsive molecules after single dose (10Gy) radiation (SDR) and FIR (2Gyx5). MCF-7 cells exposed to SDR or FIR were analyzed for alterations in gene expression using QPCR-profiling. NFkappaB DNA binding activity was analyzed using EMSA and pIkappaB using immunoblotting. Expression of TNFalpha, IL-1alpha, pAKT, IAP1, IAP2, XIAP, survivin, MnSOD, BID and Bak were determined using QPCR and/or immunoblotting. Compared to SDR, FIR significantly induced 60 genes and completely suppressed 14 genes. Furthermore, FIR induced NFkappaB-DNA binding activity and IkappaBalpha phosphorylation. Like-wise, FIR induced the expression of IAP1, IAP2, XIAP Survivin, MnSOD, TNFalpha, pAKT and IL-1alpha. The results of the study clearly show distinct differences in the molecular response of cells between SDR and FIR exposures. We identified several potential targets that may affect radio-resistance following FIR.

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Section: Discussionmentioning

confidence: 80%

NFκB activity and transcriptional responses in human breast adenocarcinoma cells after single and fractionated irradiation

Madhusoodhanan

Natarajan²,

Veeraraghavan

et al. 2009

Cancer Biology & Therapy

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“…Известно также, что хроническое облучение оказывает модифицирующее влияние на состояние иммунитета, однако роль модифицирующего влияния облучения на состояние про-и антиатерогенных факторов иммунитета изучена недостаточно. Известно, что профиль экспрессии цитокинов у лиц, подвергшихся хроническому облучению, носит в основном провоспалительный характер [18,25]. Данные о содержании цитотоксических Т-лимфоцитов (CD8 + ) противоречивы.…”

Section: проатерогенные факторы иммунитетаunclassified

Results of studying pro- and anti-atherogenic immune factors in the persons chronically exposed to ionising radiation

2021

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It is well established that cohorts of individuals exposed to ionizing radiation exhibit increased risks for cardiovascular diseases. Currently, the role of immune system in pathogenesis of atherosclerosis is actively studied. Meanwhile, the immunomodulatory effects of irradiation in pathogenesis of atherosclerosis in the persons exposed to ionizing radiation still remain unclear. The aim of this research was to study the effect of ionizing radiation upon lymphocyte subpopulations involved in pathogenesis of atherosclerosis. The lymphocyte subpopulations were studied in peripheral blood of the workers chronically exposed to occupational combined radiation versus a control group. The study considered 72 workers of the Russian nuclear production facility, the Mayak Industrial Association (mean age of 72.1±10.9 years), and 72 control individuals (mean age of 70.7±9.2 years). All the workers were chronically exposed to combined radiation (external gamma-rays and internal alpha-particles). The mean cumulative dose absorbed by red bone marrow from external gamma-ray exposure was 0.750±0.699 Gy; the mean cumulative absorbed dose to red bone marrow from internal alpha-particles was 0.072±0.092 Gy. The relative and absolute numbers of lymphocyte subpopulations (total T-cells, T-helpers, T-cytotoxic, total B-cells, NK-cells and T-NK-cells) were detected by flow cytofluorometry. The absolute number of CD3+CD19+T-lymphocytes was significantly lower in the individuals exposed to chronic irradiation, compared with the controls (1658.8±694.3 x 106/l and 1988.4±1045.4 x 106/l, respectively). The relative number of CD3+CD4+T-helpers and CD3+CD8+T-cytotoxic lymphocytes was significantly higher in individuals exposed to chronic irradiation. Relative number of T-helpers in the main group was 42.4±8.8% vs 35.3±8.7% in controls; the relative number of T-cytotoxic lymphocytes was 27.6±9.5%, and 23.3±6.5%, respectively. A significant negative correlation was revealed between absolute number of T-lymphocytes and cumulative absorbed doses to bone marrow from external gamma irradiation (correlation quotient r = -0,53565, p = 0,000001) and internal alpha sources (r = -0.54804, p = 0.0000006). This correlation may indicate a relationship between these changes (decreased absolute numbers of T cells) and occupational exposure rates. The increased relative number of T-helpers and cytotoxic T-lymphocytes confirm an assumption that specific antigens may cause an enhanced immune response during the development of atherosclerosis in exposed individuals.

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“…X-rays and c-rays are reported to increase the expression of integrin and interleukin, though the effect of proton irradiation is largely unknown [15][16][17][18][19][20][21]. The detection has been carried out by immunocytochemical staining and was analysed by laser scanning microscopy afterwards.…”

Section: Heat Shock Protein 70mentioning

confidence: 99%

DNA double strand breaks and Hsp70 expression in proton irradiated living cells

Fiedler

Reinert

Tanner

et al. 2007

Nuclear Instruments and Methods in Physics Research Section B:

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Time‐ and dose‐dependent changes of intracellular cytokine and cytokine receptor profile of Ewing tumour subpopulations under the influence of ionizing radiation

Cited by 9 publications

References 42 publications

NFκB activity and transcriptional responses in human breast adenocarcinoma cells after single and fractionated irradiation

NFκB activity and transcriptional responses in human breast adenocarcinoma cells after single and fractionated irradiation

Results of studying pro- and anti-atherogenic immune factors in the persons chronically exposed to ionising radiation

DNA double strand breaks and Hsp70 expression in proton irradiated living cells

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