Signaling factors and pathways of α-particle irradiation induced bilateral bystander responses between Seas-2B and U937 cells
Signaling factors and pathways of α-particle irradiation induced bilateral bystander responses between Seas-2B and U937 cells
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α粒子照射诱导 Seas-2B 和 U937 细胞之间双边旁观者反应的信号因子和途径
DOI：
10.1016/j.mrfmmm.2016.04.004
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发表时间：
2016-07-01
影响因子：
2.3
通讯作者：
Shao, Chunlin
中科院分区：
文献类型：
--
作者：
Fu, Jiamei;Wang, Juan;Shao, Chunlin
尽管辐射诱导的旁观者效应（里贝）已被研究了几十年，但其潜在的健康风险仍不清楚，特别是免疫系统和炎症反应在里贝中的作用。在本研究中，巨噬细胞U937细胞和上皮Beas-2B细胞共培养，以揭示旁观者信号转导因子和细胞间通讯的级联反应。在α粒子照射后，ERK和p38通路在Beas-2B细胞中被激活，并且与TNF-α和IL-8的自分泌和旁分泌信号传导相关，导致对照射细胞的直接损伤。在与α-照射的Beas-2B细胞共培养后，在旁观者U937细胞中诱导了TNF-α和IL-8的类似上调。这种上调依赖于NF-κ B B通路的激活，是α-辐射增强Beas-2 B细胞损伤的原因。有趣的是，旁观者U937细胞中TNF-α和IL-8 mRNA表达的增加明显地通过辐射Beas-2 B细胞中活化的ERK和p38途径传递，并且共培养Beas-2 B细胞中TNF-α和IL-8 mRNA的上调也部分归因于旁观者U937细胞中活化的NF-κ B途径。MEK 1/2抑制剂U 0126、p38抑制剂SB 203580和NF-κ B抑制剂BAY 11-7082预处理可明显减轻α-射线对Beas-2B细胞的损伤。我们的研究结果揭示了巨噬细胞介导的双边旁观者反应的新的信号级联，即由MAPK和NF-κ B途径调节的TNF-α和IL-8的释放协同增加α粒子照射后的细胞损伤。(C)2016爱思唯尔B. V.保留所有权利。
Although radiation induced bystander effects (RIBE) have been investigated for decades for their potential health risk, the underlying gene regulation is still largely unclear, especially the roles of immune system and inflammatory response in RIBE. In the present study, macrophage U937 cells and epithelial Beas-2B cells were co-cultured to disclose the cascades of bystander signaling factors and intercellular communications. After a-particle irradiation, both ERK and p38 pathways were activated in Beas-2B cells and were associated with the autocrine and paracrine signaling of TNF-alpha and IL-8, resulting in direct damage to the irradiated cells. Similar upregulation of TNF-alpha and IL-8 was induced in the bystander U937 cells after co-culture with a-irradiated Beas-2B cells. This upregulation was dependent on the activation of NF-kappa B pathway and was responsible for the enhanced damage of a-irradiated Beas-2B cells. Interestingly, the increased expressions of TNF-alpha and IL-8 mRNAs in the bystander U937 cells were clearly relayed on the activated ERK and p38 pathways in the irradiated Beas-2B cells, and the upregulation of TNF-alpha and IL-8 mRNAs in co-cultured Beas-2B cells was also partly due to the activated NF-kappa B pathway in the bystander U937 cells. With the pretreatment of U0126 (MEK1/2 inhibitor), SB203580 (p38 inhibitor) or BAY 11-7082 (NF-kappa B inhibitor), the aggravated damage in the a-irradiated Beas-2B cells could be largely alleviated. Our results disclosed novel signaling cascades of macrophage-mediated bilateral bystander responses that the release of TNF-alpha and IL-8 regulated by MAPK and NF-kappa B pathways synergistically increased cellular injury after a-particle irradiation. (C) 2016 Elsevier B.V. All rights reserved.