M‐CSF‐mediated macrophage differentiation but not proliferation is correlated with increased and prolonged ERK activation

M‐CSF‐mediated macrophage differentiation but not proliferation is correlated with increased and prolonged ERK activation
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M-CSF 介导的巨噬细胞分化(而非增殖)与 ERK 激活的增加和延长相关

DOI:
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发表时间:
2007
影响因子:
5.6
通讯作者:
S. Okada
S. Okada
中科院分区:
生物学2区
文献类型:
--
作者:
S. Suzu;M. Hiyoshi;Yuka Yoshidomi;H. Harada;M. Takeya;F. Kimura;K. Motoyoshi;S. Okada

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M - CSF是单核/巨噬细胞增殖和分化所必需的细胞因子。在这项研究中,我们建立了一个新的M - CSF介导的分化诱导系统,并研究了ERK的激活水平和持续时间如何先于M - CSF介导的分化。TF‐1‐fms人白血病细胞在M‐CSF的作用下迅速增殖。然而,在磷酸酯TPA的存在下,TF - 1 - fms细胞对M - CSF的反应从增殖转变为分化,这可以通过更剧烈的形态变化和更高水平的吞噬活性细胞的出现来证明。在有条件活性表达HIV - 1 Nef蛋白的TF - 1 - fms细胞中,M - CSF介导的增殖和M - CSF/TPA介导的分化均被Nef的激活所抑制。Nef活性细胞表现出ERK激活的紊乱模式。在增殖诱导条件下(无TPA),亲代细胞或Nef失活细胞在M - CSF刺激后表现出适度的ERK激活,而Nef激活细胞在增殖速率降低的情况下表现出更早和短暂的ERK激活。在诱导分化的条件下,亲本细胞或Nef失活细胞在M - CSF刺激后表现出增加和延长的ERK激活,而Nef激活细胞则表现出短暂的ERK激活。这些结果支持了ERK激活的增加和延长导致M - CSF介导的巨噬细胞分化而不是增殖的观点。j .细胞。中国生物医学工程学报,2009,31(2):519-525。©2007 Wiley‐Liss, Inc。
M‐CSF is a cytokine essential for both the proliferation and differentiation of monocytes/macrophages. In this study, we established a new M‐CSF‐mediated differentiation‐inducing system, and examined how the level and duration of the activation of ERK preceded M‐CSF‐mediated differentiation. TF‐1‐fms human leukemia cells rapidly proliferated in response to M‐CSF. However, in the presence of a phorbol ester, TPA, TF‐1‐fms cells definitely switched their responsiveness to M‐CSF from proliferation to differentiation, as evidenced by a more drastic morphological change and the appearance of cells with a higher level of phagocytic activity. In TF‐1‐fms cells expressing HIV‐1 Nef protein in a conditionally active‐manner, both M‐CSF‐mediated proliferation and M‐CSF/TPA‐mediated differentiation were inhibited by the activation of Nef. The Nef‐active cells showed perturbed patterns of ERK activation. Under the proliferation‐inducing conditions (TPA‐free), parental or Nef‐inactive cells showed modest ERK activation following M‐CSF stimulation, whereas Nef‐active cells showed an earlier and transient ERK activation, despite a decrease in their proliferation rate. Under the differentiation‐inducing conditions, parental or Nef‐inactive cells showed increased and prolonged ERK activation following M‐CSF stimulation, whereas Nef‐active cells showed transient ERK activation. These results supported the idea that the increased and prolonged ERK activation led to M‐CSF‐mediated macrophage differentiation but not to proliferation. J. Cell. Physiol. 212: 519–525, 2007. © 2007 Wiley‐Liss, Inc.
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DOI: 10.1073/pnas.87.17.6738
发表时间: 1990
影响因子: 11.1
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