The effects of p38 MAPK inhibition combined with G-CSF administration on the hematoimmune system in mice with irradiation injury.
The effects of p38 MAPK inhibition combined with G-CSF administration on the hematoimmune system in mice with irradiation injury.
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p38 MAPK 抑制联合 G-CSF 给药对辐射损伤小鼠血液免疫系统的影响。
DOI：
10.1371/journal.pone.0062921
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Meng A
中科院分区：
文献类型：
--
作者：
Li D;Wang Y;Wu H;Lu L;Wang X;Zhang J;Zhang H;Fan S;Fan F;Zhou D;Meng A
电离辐射 (IR) 引起的急性和残留（或长期）骨髓 (BM) 损伤是接受常规放疗的患者和意外暴露于中高剂量 IR 的患者的主要临床问题。在这项研究中，我们研究了 p38 抑制剂 SB203580 (SB) 和/或粒细胞集落刺激因子 (G-CSF) 治疗对小鼠模型中 IR 引起的血液免疫损伤的影响。具体而言，C57BL/6 小鼠接受亚致死剂量 (6 Gy) 的全身照射 (TBI)，然后用载体、G-CSF、SB 和 G-CSF 加 SB 进行治疗。通过腹膜内 (ip) 注射，每天两次，连续六天向小鼠施用 G-CSF（1 µg/小鼠）； SB（15 mg/kg），每隔一天腹腔注射一次，持续 10 天。结果发现，与媒介物治疗相比，SB和/或G-CSF治疗显着增强了小鼠暴露于TBI后10天和30天的各种外周血细胞计数和BM单核细胞数量的恢复。此外，与媒介物治疗对照组相比，SB和/或G-CSF治疗还增加了TBI后30天BM造血祖细胞（HPC）的克隆形成功能以及BM谱系−Sca1+c-kit+细胞（LSK细胞）和短期和长期造血干细胞（HSC）的频率。然而，SB和/或G-CSF治疗对外周血B细胞以及CD4+和CD8+T细胞的恢复没有显着影响。这些结果表明，SB 和/或 G-CSF 治疗可以部分通过促进 HSC 和 HPC 再生来减少 IR 诱导的 BM 损伤。
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.
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DOI：
10.1002/stem.5530080204
发表时间：
1990-03-01
期刊：
INTERNATIONAL JOURNAL OF CELL CLONING
影响因子：
--
作者：
PATCHEN, ML;MACVITTIE, TJ;SOUZA, LM
通讯作者：
SOUZA, LM
影响因子：
4.3
作者：
Kim, Joong-Sun;Ryoo, Seung-Bum;Yang, Kwangmo
通讯作者：
Yang, Kwangmo
影响因子：
3.7
作者：
Chen BJ;Deoliveira D;Spasojevic I;Sempowski GD;Jiang C;Owzar K;Wang X;Gesty-Palmer D;Cline JM;Bourland JD;Dugan G;Meadows SK;Daher P;Muramoto G;Chute JP;Chao NJ
通讯作者：
Chao NJ
影响因子：
20.3
作者：
Navas, Tony A.;Mohindru, Mani;Verma, Amit
通讯作者：
Verma, Amit
影响因子：
1.8
作者：
Roberts, AW
通讯作者：
Roberts, AW