title: The effects of p38 MAPK inhibition combined with G-CSF administration on the hematoimmune system in mice with irradiation injury.
abstract: The acute and residual (or long-term) bone marrow (BM) injury induced by ionizing radiation (IR) is a major clinic concern for patients receiving conventional radiotherapy and victims accidentally exposed to a moderate-to-high dose of IR. In this study, we investigated the effects of the treatment with the p38 inhibitor SB203580 (SB) and/or granulocyte colony-stimulating factor (G-CSF) on the hematoimmune damage induced by IR in a mouse model. Specifically, C57BL/6 mice were exposed to a sublethal dose (6 Gy) of total body irradiation (TBI) and then treated with vehicle, G-CSF, SB, and G-CSF plus SB. G-CSF (1 µg/mouse) was administrated to mice by intraperitoneal (ip) injection twice a day for six successive days; SB (15 mg/kg) by ip injection every other day for 10 days. It was found that the treatment with SB and/or G-CSF significantly enhanced the recovery of various peripheral blood cell counts and the number of BM mononuclear cells 10 and 30 days after the mice were exposed to TBI compared with vehicle treatment. Moreover, SB and/or G-CSF treatment also increased the clonogenic function of BM hematopoietic progenitor cells (HPCs) and the frequency of BM lineage -Sca1+c-kit+ cells (LSK cells) and short-term and long term hematopoietic stem cells (HSCs) 30 days after TBI, in comparison with vehicle treated controls. However, the recovery of peripheral blood B cells and CD4+ and CD8+ T cells was not significantly affected by SB and/or G-CSF treatment. These results suggest that the treatment with SB and/or G-CSF can reduce IR-induced BM injury probably in part via promoting HSC and HPC regeneration.
authors: Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin Key Laboratory of Molecular Nuclear Medicine, Tianjin, China.
authors: Deguan
authors: D
authors: Li
authors: Yueying
authors: Y
authors: Wang
authors: Hongying
authors: H
authors: Wu
authors: Lu
authors: L
authors: Lu
authors: Xiaochun
authors: X
authors: Wang
authors: Junling
authors: J
authors: Zhang
authors: Heng
authors: H
authors: Zhang
authors: Saijun
authors: S
authors: Fan
authors: Feiyue
authors: F
authors: Fan
authors: Daohong
authors: D
authors: Zhou
authors: Aimin
authors: A
authors: Meng
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D001772:Blood Cell Count; D001853:Bone Marrow / Q000187:drug effects* / Q000528:radiation effects*; D001854:Bone Marrow Cells / Q000187:drug effects / Q000528:radiation effects; D003114:Colony-Forming Units Assay; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D016130:Immunophenotyping; D008297:Male; D051379:Mice; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*; D011833:Radiation Injuries, Experimental / Q000276:immunology* / Q000378:metabolism*; D014916:Whole-Body Irradiation; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000954:Antigens, Surface; D007093:Imidazoles; D011725:Pyridines; D016179:Granulocyte Colony-Stimulating Factor; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580
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