RESUMEN
Interleukin 11 (IL-11) is a multifunctional cytokine isolated from bone marrow (BM)-derived stromal cells that promotes hematopoiesis and prolongs the life span of lethally irradiated animals. However, the underlying mechanism for the protective effect of IL-11 on BM is unclear. In this study, we explored the effect of IL-11 on irradiated BM cells. Freshly harvested BM cells were pretreated with 20 ng/ml of recombinant IL-11 for 30 min, irradiated with a dose of 0.5 Gy, cultured for 24 h, and then subjected to several assays. In vitro data showed that, as compared to the vehicle controls, IL-11: (1) reduced the production of reactive oxygen species; (2) reduced the alteration of mitochondrial membrane potential; (3) increased MitoTracker staining, suggesting that the number of mitochondria and their functions were better maintained; and (4) reduced apoptosis of BM cells and enhanced BM cell proliferation. In vivo studies of mice pretreated with saline or 100 µg/kg of IL-11 at 12 and 2 h before 10-Gy total body irradiation (TBI) demonstrated that G-CSF and IL-6 were significantly upregulated, whereas IL-2 and IL-4 were reduced. We found that IL-11 protects mitochondrial functions, acts with G-CSF and IL-6 to stimulate the growth of radiation-damaged BM, and reduces the immune response to radiation injury.
Asunto(s)
Médula Ósea/efectos de los fármacos , Médula Ósea/efectos de la radiación , Interleucina-11/farmacología , Mitocondrias/efectos de los fármacos , Mitocondrias/efectos de la radiación , Traumatismos Experimentales por Radiación/metabolismo , Traumatismos Experimentales por Radiación/prevención & control , Animales , Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Médula Ósea/metabolismo , Células de la Médula Ósea/metabolismo , Células de la Médula Ósea/efectos de la radiación , Procesos de Crecimiento Celular/efectos de los fármacos , Procesos de Crecimiento Celular/efectos de la radiación , Factor Estimulante de Colonias de Granulocitos/metabolismo , Interleucina-11/metabolismo , Interleucina-6/metabolismo , Masculino , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Potencial de la Membrana Mitocondrial/efectos de la radiación , Ratones , Mitocondrias/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Irradiación Corporal Total/métodosRESUMEN
Mitochondrial DNA (mtDNA) is maternally inherited and controls the oxygen-related production of adenosine-5'-triphosphate, which is transported from the mitochondria to other cellular compartments and used as energy for cellular activities. The mtDNA is physically separated from nuclear DNA (nDNA). Ionizing radiation (IR) causes the release of both mtDNA and nDNA into circulation. Our previous study demonstrated that nDNA has potential to be a biodosimeter. In this study, branched DNA technology was used to explore the alteration pattern of mtDNA after IR. C57BL/6 mice were exposed to 0, 1.5, 3, 6, 8, or 10 Gy total body irradiation; thereafter, plasma mtDNA was assessed with samples collected at 3, 6, 9, 15, 24, 48, 72, or 168 h. We found that: (1) the designed probesets were specific for mtDNA extracted from the liver, and they recognized the small amount of mtDNA mixed in the nDNA; (2) plasma mtDNA exhibited a statistically significant increase only at 6 h after 8 Gy irradiation. The alteration of mtDNA was not dose-dependent or time-dependent; hence, it is unlikely to be an effective biodosimeter.