Russian Federation
Russian Federation
Russian Federation
Russian Federation
Moscow, Russian Federation
GRNTI 76.03 Медико-биологические дисциплины
GRNTI 76.33 Гигиена и эпидемиология
OKSO 14.04.02 Ядерные физика и технологии
OKSO 31.06.2001 Клиническая медицина
OKSO 31.08.08 Радиология
OKSO 32.08.12 Эпидемиология
BBK 51 Социальная гигиена и организация здравоохранения. Гигиена. Эпидемиология
BBK 534 Общая диагностика
TBK 5708 Гигиена и санитария. Эпидемиология. Медицинская экология
TBK 5712 Медицинская биология. Гистология
TBK 5734 Медицинская радиология и рентгенология
TBK 6212 Радиоактивные элементы и изотопы. Радиохимия
The products of radiolysis released from cellular compartment under the influence of ionizing radiation: highly mobile groups of proteins, damaged nuclear and mitochondrial DNA, extracellular ATP and oxidized low density lipoproteins, cause stress activation in irradiated tissues through a pattern of the receptors with start of the cascade r53 and NF-κB of pro-inflammatory ways conducting to an expression of pro-inflammatory genes stimulating synthesis of cytokines of the IL-1 family. Excessive activation of pro-inflammatory way under the influence of a radioactive stress is limited to synthesis, anti-inflammatory cytokines: IL-4, IL-10, IL-11, IL-13 and also antagonists of IL-1 receptor and TGF-β. G-CSF and MG-CSF induced by action of pro-inflammatory cytokines have anti-inflammatory and anti-apoptotic properties decreasing level of pro-inflammatory cytokines IL-6 and TNF. Glucocorticoids participate in regulation of primary radioactive stress, suppressing an excessive expression of genes of pro-inflammatory cytokines. Increased IL-1 level stimulates secretion of corticosteroids through mechanism of feedback. Adrenergic stimulation is capable to raise a gene IL-1β expression. The mechanism of radiation apoptosis of stem cells is implemented through p53-Puma way which blocks interaction anti-apoptotic proteins of Bcl-2 with pro-apoptotic proteins of Bax and Bak. After release from mitochondrion of cytochrome C and apoptosis-inducing factor there is an activation of effector caspases: caspases 3, 6 and 7 through caspase 9, and final cell destruction. Wnt way is crucial for post-radiation repair. Potential of the regenerative response of hemopoietic tissue to radiation injury depends on catenin and ability of Wnt way to stimulate post-radiation bone marrow reparation. Mesenchymal stem cells of bone marrow play a large role in post-radiation regeneration of hemopoietic tissue. Their main action is carried out through TLR2 and TLR4 receptors. Mobilization of hemopoietic stem cells is bound to release proteases from bone marrow, including neutrophil elastase and cathepsin G, and a matrix metalproteinase-9. Radioprotective properties of exogenous IL-1 aren’t limited only by induction of raised G-CSF and GM-CSF production. The larger role in radiation protection is played by the reaction induced by IL-1 in the form of feedback with production anti-apoptotic and anti-inflammatory factors. Primary radioactive stress limits time of radiomitigable effect of IL-1 by 1-2 h after its application after radiation.
primary radiation stress, proinflammatory cytokines, interleukin-1β, anti-inflammatory cytokines, granulocyte-colony stimulating factor, postradiation blood reparation
1. Grebenyuk AN, Legeza VI. Radioprotective properties of interleukin-1. Saint-Petersburg: Foliant. 2012. 216 p. Russian.
2. Wu SG, Miyamoto T. Radioprotection of the intestinal crypts of mice by recombinant human interleukin-1 alpha. Radiat Res. 1990;123(1):12-115.
3. Ilyin LA, Rudnii NM, Suvorov NN, et al. Indralin - radioprotector of emergency action. Radioprotective properties, pharmacology, mechanism of the action, clinic. Moscow. 1994. 436 p. Russian.
4. Vasin MV, Ushakov IB, Kovtun VYu, et al. The characteristic of radioprotective properties of radioprotector B-190 at its administration after irradiation. Radiation Biology. Radioecology. 2008;48(6):730-733. Russian.
5. Vasin MV, Ushakov IB, Kovtun VYu, et al. Radioprotective properties of radioprotector of indralin emergency action at its administration after irradiation in the condition of partial shielding of rat abdomen. Radiation Biology. Radioecology. 2008;48(2):199-201. Russian.
6. Gluzman-Poltorak Z, Vainstein V, Basile LA. Recombinant interleukin-12, but not granulocyte-colony stimulating factor, improves survival in lethally irradiated nonhuman primates in the absence of supportive care: evidence for the development of a frontline radiation medical countermeasure. Amer J Hematol. 2014;89(9):868-873.
7. Rozhdestvenskii LM, Shliakova TG, Schegoleva RA, et al. The estimation of radioprotective medical efficacy of recombinant trombopoietin in dogs by criteria of hemopoiesis and survival. Radiation Biology. Radioecology. 2013;53(3):280-289. Russian.
8. Grebenyuk AN, Zatsepin VV, Aksenova NV, et al. The influence of serial application of B-190 and interleukin-1β to survival and bone marrow hemopoiesis of irradiated mice. Radiation Biology. Radioecology. 2010;50(4):175-180. Russian.
9. Jang SS, Park WY. The combined effects of amifostine and Interleukin 1 beta (IL-1beta) on radiation-induced gastrointestinal and hematopoietic Injury. Cancer Res. Treat. 2003;35(6) 528-532.
10. Lukashin BP, Sofronov GA. Radioprotective effect of cystamine and heparin in experiments on mice with different resistance. Bull. exp. biol. med. 1996;121(5):544-546. Russian.
11. Venereau E, Ceriotti C, Bianchi ME. DAMPs from cell death to new life. Front. Immunol. 2015;6:422.
12. Vasin MV, Chernov YuN. Radiation influence to circulative immune complex in rats’ blood. Radiobiology. 1991;31(3):365-367. Russian.
13. Schaue D, Kachikwu EL, McBride WH. Cytokines in radiobiological responses: a review. Radiat Res. 2012;178(6):505-523.
14. Xiao M. The role of proinflammatory cytokine interleukin-18 in radiation injury. Health Phys. 2016;111(2):212-217.
15. Kim SJ, Choe H, Lee GJ, et al. Ionizing radiation induces innate immune responses in macrophages by generation of mitochondrial reactive oxygen species. Radiat Res. 2017;187(1):32-41.
16. Linard C, Marquette C, Mathieu J, et al. Acute induction of inflammatory cytokine expression after gamma-irradiation in the rat: effect of an NF-kappaB inhibitor. Int J Radiat Oncol Biol Phys. 2004;58(2):427-434.
17. Cohen I, Rider P, Vornov E, et al. IL-1α is a DNA damage sensor linking genotoxic stress signaling to sterile inflammation and innate immunity. Sci Rep. 2015;5:14756.
18. Carta S, Lavieri R, Rubartelli A. Different members of the IL-1 family come out in different ways: DAMPs vs. cytokines?. Front. Immunol 2013;4:123
19. Stoecklein VM, Osuka A, Ishikawa S, et al. Radiation exposure induces inflammasome pathway activation in immune cells. J. Immunol. 2015;194(3):1178-1189.
20. Vince JE, Silke J. The intersection of cell death and inflammasome activation. Cell Mol Life Sci. 2016;73(11-12):2349-2367.
21. de Vasconcelos NM, Van Opdenbosch N, Lamkanfi M. Inflammasomes as polyvalent cell death platforms. Cell Mol Life Sci. 2016;73(11-12):2335-2347.
22. Sharma D, Kanneganti TD. The cell biology of inflammasomes: Mechanisms of inflammasome activation and regulation. J Cell Biol. 2016;213(6):617-629.
23. Moroni M, Lombardini E, Salber R, et al. Hematological changes as prognostic indicators of survival: similarities between Göttingen minipigs, humans, and other large animal models. PLoS ONE. 2011;6, e25210
24. Chwee JY, Khatoo M, Tan NYJ, Gasser S. Apoptotic cells release IL1 receptor antagonist in response to genotoxic stress. Cancer Immunol Res. 2016;4(4):294-302.
25. Shonai T, Adachi M, Sakata K, et al. MEK/ERK pathway protects ionizing radiation-induced loss of mitochondrial membrane potential and cell death in lymphocytic leukemia cells. Cell Death Differ. 2002;9(9):963-971.
26. Di Maggio FM, Minafra L, Forte GI, et al. Portrait of inflammatory response to ionizing radiation treatment. J Inflamm. (Lond). 2015;12:14.
27. Redondo-Castro E, Cunningham C, Miller J, et al. Interleukin-1 primes human mesenchymal stem cells towards an anti-inflammatory and pro-trophic phenotype in vitro. Stem Cell Res Ther. 2017;8(1):79. DOI:https://doi.org/10.1186/s13287-017-0531-4.
28. Kim JS, Yang M, Lee CG, et al. In vitro and in vivo protective effects of granulocyte colony-stimulating factor against radiation-induced intestinal injury. Arch Pharm Res. 2013;36(10):1252-1261. DOI:https://doi.org/10.1007/s12272-013-0164-9.
29. Singh VK, Fatanmi OO, Singh PK, Whitnall MH. Role of radiation-induced granulocyte colony-stimulating factor in recovery from whole body gamma-irradiation. Cytokine. 2012;58(3):406-4014. DOI:https://doi.org/10.1016/j.cyto.2012.03.011.
30. Beetz A, Messer G, Oppel T, et al. Induction of interleukin 6 by ionizing radiation in a human epithelial cell line: control by corticosteroids. Int J Radiat Biol. 1997;72(1):33-43.
31. Morrissey PJ, Charrier K, Alpert A, Bressler L. In vivo administration of IL-1 induces thymic hypoplasia and increased levels of serum corticosterone. [in 3 h]. J Immunol. 1988;141(5):1456-1463.
32. Petrov RV. The role of hormone and mediators in immune system function. Vest. AMN USSR. 1980(8):3-9. Russian.
33. Bodey B. Neuroendocrine influence on thymic haematopoiesis via the reticulo-epithelial cellular network. Expert Opin Biol Ther. 2002;6(1):57-72.
34. von Vietinghoff S, Ley K. Homeostatic regulation of blood neutrophil counts. J Immunol. 2008;181(8):5183-5188.
35. Marković L. [Interaction involving the thymus and the hypothalamus-pituitary axis, immunomodulation by hormones]. Srp Arh Celok Lek. 2004. Vol. 132(5-6):187-193.
36. Bodey B. Thymic reticulo-epithelial cells: key cells of neuroendocrine regulation. Expert Opin Biol Ther. 2007;7(7):939-949.
37. Bezin GI, Moroz BB. The factors controlled stem cell recirculation. The modification of endogenous glucocorticoid effect on CFU migration with T-defect mice. Radiobiology. 1983;23(3):328-331. Russian.
38. Shao L, Luo Y, Zhou D. Hematopoietic stem cell injury induced by ionizing radiation. Antioxid Redox Signal. 2014;20(9):1447-1462. DOI:https://doi.org/10.1089/ars.2013.5635.
39. Meng A, Wang Y, Brown S.A, et al. Ionizing radiation and busulfan inhibit murine bone marrow cell hematopoietic function via apoptosis-dependent and -independent mechanisms. Exp Hematol. 2003;31(12):1348-1356.
40. Halestrap AP. Calcium, mitochondria and reperfusion injury: a pore way to die. Biochem Soc Trans. 2006;34. Pt 2:232-237.
41. Green DR, Kroemer G. The pathophysiology of mitochondrial cell death. Science. 2004;305(5684):626-629.
42. Michels J, Johnson PW, Packham G. Mcl-1. Int J Biochem. Cell Biol. 2005;37(2):267-271.
43. Germain M, Milburn J, Duronio V. MCL-1 inhibits BAX in the absence of MCL-1/BAX Interaction. J Biol Chem. 2008;283(10):384-392.
44. Giorgi C, Missiroli S, Patergnani S, et al. Mitochondria-Associated Membranes: Composition, Molecular Mechanisms, and Physiopathological Implications. Antioxid Red Signaling. 2015;22(12):995-1019.
45. Shao L, Sun Y, Zhang Z, et al. Deletion of proapoptotic Puma selectively protects hematopoietic stem and progenitor cells against high-dose radiation. Blood. 2010;115(23. 4707-4714.
46. Yu H, Shen H, Yuan Y, et al. Deletion of Puma protects hematopoietic stem cells and confers long-term survival in response to high-dose gamma-irradiation. Blood. 2010;115(17):3472-3480.
47. Friedlander RM, Gagliardini V, Rotello RJ, Yuan J. Functional role of interleukin 1 beta [IL-1 beta] in IL-1 beta-converting enzyme-mediated apoptosis. J Exp Med. 1996;184(2):717-724.
48. Mulroy T, McMahon JA, Burakoff SJ, et al. Wnt-1 and Wnt-4 regulate thymic cellularity. Eur J Immunol. 2002;32(4):967-971.
49. Fernandez A, Huggins I.J, Perna L, et al. The WNT receptor FZD7 is required for maintenance of the pluripotent state in human embryonic stem cells. Proc Natl Acad. Sci. USA. 2014;111(4):1409-1414.
50. Miyamoto K, Araki KY, Naka K, et al. Foxo3a is essential for maintenance of the hematopoietic stem cell pool. Cell Stem Cell. 2007;1(1):101-112.
51. Essers MA, de Vries-Smits LM, Barker N, et al. Functional interaction between beta-catenin and FOXO in oxidative stress signaling. Science. 2005;308(5725):1181-1184.
52. Lento W, Ito T, Zhao C, et al. Loss of β-catenin triggers oxidative stress and impairs hematopoietic regeneration. Genes Dev. 2014;28(9):995-1004. DOI:https://doi.org/10.1101/gad.231944.113.
53. Miller TW, Soto-Pantoja DR, Schwartz AL, et al. CD47 receptor globally regulates metabolic pathways that control resistance to ionizing radiation. J Biol Chem. 2015;290(41):24858-24874. DOI:https://doi.org/10.1074/jbc.M115.665752.
54. Kozlov VA. Intracellular factors regulating activity of hemopoietic stem cells. Bull Exp Biol Med. 2005;139(1):106-113.
55. Steingen C, Brenig F, Baumgartner L, et al. Characterization of key mechanisms in transmigration and invasion of mesenchymal stem cells. J Mol Cell Cardiol. 2008;44(6):1072-1084. DOI:https://doi.org/10.1016/j.yjmcc.2008.03.010
56. Gao P, Tchernyshyov I, Chang T.C, et al. c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism. Nature. 2009;458(7239):762-765.
57. Gaugler MH, Squiban C, Mouthon MA, et al. Irradiation enhances the support of haemopoietic cell transmigration, proliferation and differentiation by endothelial cells. Br J Haematol. 2001;113(4):940-950.
58. Nishida C, Kusubata K, Tashiro Y.et al. MT1-MMP plays a critical role in hematopoiesis by regulating HIF-mediated chemokine/cytokine gene transcription within niche cells. Blood. 2012;119(23):5405-5416. DOI:https://doi.org/10.1182/blood-2011-11-390849.
59. Till JE, McCullouch EA. A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Radiat Res. 1961;14(2):213-222.
60. Ponte AL, Ribeiro-Fleury T, Chabot V, et al. Granulocyte-Colony-Stimulating Factor Stimulation of Marrow Mesenchymal Stromal Cells Promotes CD34+ Cell Migration Via a Matrix Metalloproteinase-2-Dependent Mechanism. Stem Cells Dev. 2012;21(17):3162-3172. DOI:https://doi.org/10.1089/scd.2012.0048
61. Porter SN, Cluster AS, Signer RAJ, et al. Cell Autonomously Modulates the Hematopoietic Stem Cell Response to Inflammatory Cytokine. Stem Cell Reports. 2016;6(6):806-914.
62. Nowlan B, Futrega K, Brunck M.E, et al. HIF-1α stabilizing agent FG-4497 rescues human CD34+ cell mobilization in response to G-CSF in immuno-deficient mice. Exp. Hematol. 2017;52:50-55. DOI:https://doi.org/10.1016/j.exphem.2017.05.004.
63. Rafii S, Mohle R, Shapiro F, et al. Regulation of hematopoiesis by microvascular endothelium. Leuk. Lymphoma. 1997;27(5-6):375-386.
64. Heissig B, Ohki Y, Sato Y, et al. A role for niches in hematopoietic cell development. Hematology. 2005;10(3):247-253.
65. Wang X, Cheng Q, Li L, et al. Toll-like receptors 2 and 4 mediate the capacity of mesenchymal stromal cells to support the proliferation and differentiation of CD34⁺ cells. Exp. Cell Res. 2012;318(3):196-206. DOI:https://doi.org/10.1016/j.yexcr.2011.11.001.
66. Neta R, Vogel SN, Oppenheim JJ, Douches SD. Cytokines in radioprotection. Comparison of the radioprotective effects of IL-1 to IL-2, GM-CSF and IFN gamma. Lymphokine Res. 1986;5. Suppl 1:105-110.
67. Neta R, Oppenheim JJ, Douches SD. Interdependence of the radioprotective effects of human recombinant interleukin 1 alpha, tumor necrosis factor alpha, granulocyte colony-stimulating factor, and murine recombinant granulocyte-macrophage colony-stimulating factor. J Immunol. 1988;140(1):108-111.
68. Neta R, Oppenheim J.J. Cytokines in therapy of radiation injury. Blood. 1988;72(3):1093-1095.
69. Legeza VI, Chigareva NG, Abdul YuA, Galeev ISh. Cytokines as agents of early pathogenesis therapy of radiation injuries. Their efficacy and mechanism of action. Radiation Biology. Radioecology. 2000;40(4):420-424. Russian.
70. Rozhdestvenskiy LM, Korovkina EP, Deshovoy YuB. The application of recombinant human interleukin-1beta (betaleukin) for a treatment of heavy degree of acute radiation syndrome with dogs. Radiation Biology. Radioecology. 2008;48(2):185-194. Russian.
71. Reimers J, Wogensen LD, Welinder B, et al. The pharmacokinetics, distribution and degradation of human recombinant interleukin 1 beta in normal rats. Scand. J. Immunol. 1991;34(5):597-610.
72. Grebenyuk AN, Aksenova NV, Zastepin VV, et al. The influence of B-190 and interleukin to a dynamic of peripheral blood cell count and function status of neutrophil of irradiated mice. Radiation Biology. Radioecology. 2013;53(3):290-295. Russian.
73. van Os R, Lamont C, Witsell A, Mauch P.M. Radioprotection of bone marrow stem cell subsets by interleukin-1 and kit-ligand: implications for CFU-S as the responsible target cell population. Exp. Hematol. 1997;25(3):205-210.
74. Legeza VI, Chigareva VI, Petkevich IV, et al. Experimental study of interleukin-1beta efficacy at radiation injuries. Hematol. Transfusiol. 1995;40(3):10-13. Russian.
75. Rozhdestvenskiy LM, Deshovoy YuB, Lebedev VG, Nesterova T.A. The dependence of therapy efficacy of interleukin-1β from time of its adminisration on mice after ionizing irradiation. Radiation Biology. Radioecology. 2002;42(1):65-69. Russian.
76. Linard C, Marquette C, Clarençon D, et al. Acute ileal inflammatory cytokine response induced by irradiation is modulated by subdiaphragmatic vagotomy. J Neuroimmunol. 2005;168(1-2):83-95.
77. Bigildeev AE, Zezina EA, Drize NJ. The effects of interleukin-1 beta and gamma-quantum braking radiation on mesenchymal progenitor cells. Mol Biol. 2017;51(3):393-403.
78. Hancock SL, Chung RT, Cox RS, Kallman RF. Interleukin 1 beta initially sensitizes and subsequently protects murine intestinal stem cells exposed to photon radiation. Cancer Res. 1991;51(9):2280-2285.
79. Ulyanova LP, Ketlinskiy SA, Budagov RS. The study of interleukin-1beta efficacy with treatment of combined radiation-thermic injuries. Radiation Biology. Radioecology. 1997;37(2):175-181. Russian.
80. Fu Y, Wang Y, Du L, et al. Resveratrol inhibits ionising irradiation-induced inflammation in MSCs by activating SIRT1 and limiting NLRP-3 inflammasome activation. Int J Mol Sci. 2013;14(7):14105-14118. DOI:https://doi.org/10.3390/ijms140714105.
81. Singh VK, Grace MB, Parekh VI, et al. Effects of genistein administration on cytokine induction in whole-body gamma irradiated mice. Int. Immunopharmacol. 2009;9(12):1401-1410. DOI:https://doi.org/10.1016/j.intimp.2009.08.012.
82. Ha CT, Li XH, Fu D, et al. Genistein nanoparticles protect mouse hematopoietic system and prevent proinflammatory factors after gamma irradiation. Radiat Res. 2013;180(3):316-325. DOI:https://doi.org/10.1667/RR3326.1.
83. Vasin MV, Ushakov IB, Kovtun VYu, et al. The influence of combined application of quercetin and indralin to post-radiation repair of hemopoiesis with acute radiation syndrome. Radiation Biology. Radioecology. 2011;51(2):247-251. Russian.
84. Fibbe WE, van Damme J, Billiau A, et al. Interleukin 1 induces human marrow stromal cells in long-term culture to produce granulocyte colony-stimulating factor and macrophage colony-stimulating factor. Blood. 1988;71(2):430-435.
85. Lebedev VG, Moroz BB, Deshovoy YuB, Rozhdestvenskiy LM. The study of radioprotective effect of mechanism of radioprotective effect of interleukin-1β with long-lived-culture of bone marrow. Radiation Biology. Radioecology. 2002;42(1):60-64. Russian.
86. Lebedev VG, Moroz BB, Deshovoy YuB, Lyrschikova AV. The study of hemopoiesis-induced microenviroment in the mechanism of radioprotective action of interleukin-1ß on the model of long-lived culture of bone marrow. Radiation Biology. Radioecology. 2004;44(2):170-175. Russian.
87. Hosoi Y, Kurishita A, Ono T, Sakamoto K. Effect of recombinant human granulocyte colony-stimulating factor on survival in lethally irradiated mice. Acta Oncol. 1992;31(1):59-63.
88. Rozhdestvenskiy LM, Schegoleva RA, Deshovoy YuB, et al. Comparative assessment of medical efficacy of different preparations of granulocyte colony-stimulated factor in experiments on irradiated mice. Radiation Biology. Radioecology. 2012;52(5):503-509. Russian.
89. Rozhdestvenskiy LM, Shliakova TG, Schegoleva RA, et al. Assessment of medical efficacy of domestic agents of G-CSF in experiment on irradiated dogs. Radiation Biology. Radioecology. 2013;(1)47-54. Russian.
90. Farese AM, Cohen MV, Katz BP, et al. Filgrastim improves survival in lethally irradiated nonhuman primates. Radiat Res. 2013;179(1):89-100. DOI:https://doi.org/10.1667/RR3049.1.
91. Seligovkin GD, Barabanova AV. Therapy of acute radiation syndrome from uniform and non-uniform irradiation. Radiation medicine. Ed. L.A. Ilyin. - Moscow: Izd.AT. 2001. Vol. 2. P. 108-129. Russian.
