Regulation of IL-27 p28 gene expression in macrophages through MyD88- and interferon-gamma-mediated pathways.
Regulation of IL-27 p28 gene expression in macrophages through MyD88- and interferon-gamma-mediated pathways.
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DOI：
10.1084/jem.20061440
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发表时间：
2007-01-22
影响因子：
15.3
通讯作者：
Ma, Xiaojing
中科院分区：
文献类型：
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作者：
Liu, Jianguo;Guan, Xiuqin;Ma, Xiaojing
白介素27(IL-27)是由EB病毒诱导基因3和p28链组成的异二聚体细胞因子家族的最新成员。IL-27不仅在调节幼稚T辅助细胞分化中发挥重要作用，而且具有抗炎作用。IL-27是单核/巨噬细胞和树突状细胞活化的早期产物。然而，炎症信号刺激IL-27产生的机制还没有被探索。在本研究中，我们研究了脂多糖和干扰素-γ对巨噬细胞中小鼠IL-27p28基因转录的调节作用。我们发现，脂多糖刺激的p28的产生完全依赖于Toll样受体4/髓系分化因子88(MyD88)介导的途径，但仅部分依赖于核因子κB、c-Rel。干扰素-γ诱导的p28的产生/分泌也部分依赖于MyD88，但不依赖于c-Rel。然后，我们克隆了小鼠p28基因启动子，并定位了其多个转录起始点。此外，我们确定了关键的启动子元件，它们分别以c-Rel和干扰素调节因子1依赖的方式分别介导脂多糖和干扰素-γ对p28基因转录的诱导作用。
Interleukin (IL)-27 is the newest member of the IL-12 family of heterodimeric cytokines composed of the Epstein-Barr virus–induced gene 3 and p28 chains. IL-27 not only plays an important role in the regulation of differentiation of naive T helper cells but also possesses antiinflammatory properties. IL-27 is an early product of activated monocytes/macrophages and dendritic cells. However, the mechanisms whereby inflammatory signals stimulate IL-27 production have not been explored. In this study, we investigated the transcriptional regulation of the mouse IL-27 p28 gene in macrophages in response to lipopolysaccharide (LPS) and interferon (IFN)-γ. We found that LPS-stimulated p28 production was completely dependent on the Toll-like receptor 4/myeloid differentiation factor 88 (MyD88)–mediated pathway but only partially dependent on nuclear factor κB c-Rel. IFN-γ–induced p28 production/secretion was also partially dependent on MyD88 but independent of c-Rel. We then cloned the mouse p28 gene promoter and mapped its multiple transcription initiation sites. Furthermore, we identified critical promoter elements that mediate the inductive effects of LPS and IFN-γ, separately and synergistically, on p28 gene transcription in a c-Rel– and interferon regulatory factor 1–dependent manner, respectively.