Erythropoietin-dependent autocrine secretion of tumor necrosis factor-alpha in hematopoietic cells modulates proliferation via MAP kinase-ERK-1/2 and does not require tyrosine docking sites in the EPO receptor
Erythropoietin-dependent autocrine secretion of tumor necrosis factor-alpha in hematopoietic cells modulates proliferation via MAP kinase-ERK-1/2 and does not require tyrosine docking sites in the EPO receptor
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DOI：
10.1016/j.yexcr.2004.04.009
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发表时间：
2004-08-01
影响因子：
3.7
通讯作者：
Sawyer, ST
中科院分区：
文献类型：
--
作者：
Chen, J;Jacobs-Helber, SM;Sawyer, ST
原代红系细胞和红系细胞系在用促红细胞生成素（EPO）刺激后可合成并分泌肿瘤坏死因子-α（TNF-α）。在红白血病和骨髓细胞系HCD 57、DA 3-EPOR和BAF 3-EPOR中研究了触发TNF-α合成和分泌的作用。EPO诱导的膜结合形式的自分泌TNF-α似乎增强了HCD 57和DA 3-EPOR细胞的增殖;然而，分泌的自分泌/旁分泌TNF-α的浓度从来不足以产生效果。自分泌TNF-α通过TNFRII受体起作用以刺激增殖。自分泌TNF-α的膜结合形式对丝裂原活化蛋白激酶（MAPK）/细胞外信号相关激酶（ERK-1/2）活性的调节在HCD 57和DA 3-EPOR细胞的EPO依赖性增殖控制中发挥了重要作用。发现原代红系细胞和DA 3-EPOR细胞表达相似的高水平TNFRI和TNFRII，表明TNF-α受体的差异表达不能解释为什么原代细胞被自分泌TNF-α抑制而DA 3-EPOR细胞被自分泌TNF-α刺激。BAF 3细胞表达的突变EPOR没有细胞质酪氨酸残基能够触发EPO依赖性TNF-α的合成和分泌，表明EPOR中的酪氨酸停靠位点不是EPO依赖性TNF-α分泌所必需的。(C)2004年爱思唯尔公司All rights reserved.
Primary erythroid cells and erythroid cell lines may synthesize and secrete tumor necrosis factor-alpha (TNF-alpha) following stimulation with erythropoietin (EPO). The effect of triggering TNF-alpha synthesis and secretion was investigated in erythroleukemia and myeloid cell lines: HCD57, DA3-EPOR, and BAF3-EPOR. The EPO-induced, membrane-bound form of autocrine TNF-alpha seemed to enhance proliferation of HCD57 and DA3-EPOR cells; however, the concentration of secreted autocrine/paracrine TNF-alpha was never sufficient to have an effect. Autocrine TNF-alpha acts through TNFRII receptors to stimulate proliferation. Modulation of mitogen-activated protein kinase (MAPK)/extracellular signal-related kinase (ERK-1/2) activity by the membrane-bound form of autocrine TNF-alpha apparently played a central role in the control of EPO-dependent proliferation of HCD57 and DA3-EPOR cells. Primary erythroid cells and DA3-EPOR cells were found to express similar, high levels of both TNFRI and TNFRII, showing that differential expression of TNF-alpha receptors does not explain why primary cells are inhibited and DA3-EPOR cells are stimulated by autocrine TNF-alpha. BAF3 cells expressing a mutant EPOR with no cytoplasmic tyrosine residues were capable of triggering EPO-dependent TNF-alpha synthesis and secretion, indicating that tyrosine-docking sites in the EPOR were not required for EPO-dependent TNF-alpha secretion. (C) 2004 Elsevier Inc. All rights reserved.