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SCL转录因子以及白血病抑制因子、抑瘤素M和白细胞介素-6对巨噬细胞分化的差异调节

The SCL transcription factor and differential regulation of macrophage differentiation by LIF, OSM and IL-6.

作者信息

Begley C G

机构信息

Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.

出版信息

Stem Cells. 1994;12 Suppl 1:143-9; discussion 149-51.

PMID:7696958
Abstract

The SCL gene is a member of the helix-loop-helix family of transcription factors. First identified because of its involvement in a rare chromosome translocation in human T cell acute lymphoblastic leukemia, it is now recognized to be involved in up to 25% of T cell leukemias. Normally within the hemopoietic system the gene is expressed in progenitor cells, erythroid cells, mast cells and megakaryocytes. During macrophage differentiation the level of SCL mRNA and protein becomes undetectable. To examine this further, SCL was over expressed in murine M1 cells. This resulted in perturbation of macrophage differentiation induced by leukemia inhibitory factor (LIF) and oncostatin-M (OSM) but not interleukin (IL)-6. Moreover the perturbation of LIF-induced differentiation applied to some components of macrophage differentiation but not others. This suggests that signaling through the gp130 homodimer (as occurs with IL-6) does not utilize an SCL-inhibitable pathway. In contrast the LIF receptor/gp130 heterodimer does utilize an SCL-inhibitable pathway for some elements of macrophage differentiation (e.g., lysozyme induction) but not others (e.g., M-CSF receptor induction).

摘要

SCL基因是转录因子螺旋-环-螺旋家族的成员。它最初是由于参与人类T细胞急性淋巴细胞白血病中一种罕见的染色体易位而被发现,现在已知它与高达25%的T细胞白血病有关。在正常造血系统中,该基因在祖细胞、红细胞、肥大细胞和巨核细胞中表达。在巨噬细胞分化过程中,SCL mRNA和蛋白质的水平变得无法检测到。为了进一步研究这一点,SCL在小鼠M1细胞中过表达。这导致白血病抑制因子(LIF)和制瘤素-M(OSM)诱导的巨噬细胞分化受到干扰,但白细胞介素(IL)-6诱导的分化不受影响。此外,LIF诱导的分化干扰作用于巨噬细胞分化的某些成分,而非其他成分。这表明通过gp130同二聚体的信号传导(如IL-6所发生的那样)不利用SCL可抑制的途径。相反,LIF受体/gp130异二聚体在巨噬细胞分化的某些成分(如溶菌酶诱导)中确实利用了SCL可抑制的途径,但在其他成分(如M-CSF受体诱导)中则不然。

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The SCL transcription factor and differential regulation of macrophage differentiation by LIF, OSM and IL-6.SCL转录因子以及白血病抑制因子、抑瘤素M和白细胞介素-6对巨噬细胞分化的差异调节
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