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首页> 外文期刊>Molecular and Cellular Biology >Regulation of interleukin 12 p40 expression through an NF-kappa B half-site.
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Regulation of interleukin 12 p40 expression through an NF-kappa B half-site.

机译:通过NF-κB半位点调节白介素12 p40表达。

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Interleukin 12 (IL-12) is an inducible cytokine composed of 35- and 40-kDa subunits that is critical for promoting T helper type 1 development and cell-mediated immunity against pathogens. The 40-kDa subunit, expressed by activated macrophages and B cells, is induced by several pathogens in vivo and in vitro and is augmented or inhibited by gamma interferon (IFN-gamma) or IL-10, respectively. Control of IL-12 p40 expression is therefore important for understanding resistance and susceptibility to a variety of pathogens, including Leishmania major and perhaps human immunodeficiency virus. In this report, we provide the first characterization of IL-12 p40 gene regulation in macrophages. We localize inducible activity of the promoter to the sequence -122GGGGAATTTTA-132 not previously recognized to bind Rel family transcription factors. We demonstrate binding of this sequence to NF-kappa B (p50/p65 and p50/c-Rel) complexes in macrophages activated by several p40-inducing pathogens and provide functional data to support a role for NF-kappa B family members in IL-12 p40 activation. Finally, we find that IFN-gamma treatment of cells enhances this binding interaction, thus potentially providing a mechanism for IFN-gamma augmentation of IL-12 production by macrophages.
机译:白细胞介素12(IL-12)是由35-kDa和40-kDa亚基组成的诱导型细胞因子,对促进1型T辅助细胞的发育和细胞介导的针对病原体的免疫至关重要。由活化的巨噬细胞和B细胞表达的40 kDa亚基在体内和体外被多种病原体诱导,分别被γ干扰素(IFN-γ)或IL-10增强或抑制。因此,控制IL-12 p40的表达对于理解对多种病原体(包括利什曼原虫和也许是人类免疫缺陷病毒)的抵抗力和敏感性很重要。在本报告中,我们提供了巨噬细胞中IL-12 p40基因调控的第一个特征。我们将启动子的诱导活性定位于先前未认识到与Rel家族转录因子结合的序列-122GGGGAATTTTA-132。我们证明了该序列与巨噬细胞中由几种诱导p40的病原体激活的NF-κB(p50 / p65和p50 / c-Rel)复合物的结合,并提供功能数据来支持IL-中NF-κB家族成员的作用。 12 p40激活。最后,我们发现细胞的IFN-γ处理可增强这种结合相互作用,从而潜在地为巨噬细胞提供IFN-γ增强IL-12产生的机制。

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