Gruss H J, Brach M A, Herrmann F
Department of Internal Medicine I, University of Freiburg Medical Center, Germany.
Blood. 1992 Nov 15;80(10):2563-70.
Recent studies have indicated that the leukemia inhibitory factor (LIF) induces secretion of interleukin-6 (IL-6) in myeloid cells. We here show that synthesis of IL-6 by human mononuclear phagocytes exposed to recombinant human (rh) LIF is preceded by an increase of IL-6 transcript levels as a result of transcriptional activation of the IL-6 gene. Analysis of deleted fragments of the IL-6 promoter indicated that transcriptional activation of the IL-6 promoter was associated with enhanced binding activity of the transcription factor nuclear factor (NF)-kappa B. Binding of activation protein (AP)-1 and NF-IL-6, also known to transcriptionally activate the IL-6 promoter, was not inducible by LIF. Furthermore, introduction of the NF-kappa B sequence into a heterologous promoter construct, but not of AP-1- and NF-IL-6-binding sequences, conferred inducibility by LIF to this promoter. Deletion of the NF-kappa B binding site in the IL-6 promoter was associated with loss of inducibility by LIF, lending further support for the notion that the NF-kappa B binding site is crucial for LIF-mediated induction of the IL-6 promoter. Taken together, our results show that rhLIF induces IL-6 gene expression in mononuclear phagocytes through transcriptional gene activation involving NF-kappa B.
最近的研究表明，白血病抑制因子（LIF）可诱导髓系细胞分泌白细胞介素-6（IL-6）。我们在此表明，暴露于重组人（rh）LIF的人单核吞噬细胞合成IL-6之前，由于IL-6基因的转录激活，IL-6转录水平会升高。对IL-6启动子缺失片段的分析表明，IL-6启动子的转录激活与转录因子核因子（NF）-κB的结合活性增强有关。激活蛋白（AP）-1和NF-IL-6的结合，也已知可转录激活IL-6启动子，但不能被LIF诱导。此外，将NF-κB序列引入异源启动子构建体中，而不是引入AP-1和NF-IL-6结合序列，可使该启动子具有LIF诱导性。IL-6启动子中NF-κB结合位点的缺失与LIF诱导性的丧失有关，这进一步支持了NF-κB结合位点对LIF介导的IL-6启动子诱导至关重要的观点。综上所述，我们的结果表明，rhLIF通过涉及NF-κB的转录基因激活在单核吞噬细胞中诱导IL-6基因表达。
