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首页> 外文期刊>Cytokine >Differential response of the murine IL-12 p35 gene to lipopolysaccharide compared with interferon-gamma and CD40 ligation.
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Differential response of the murine IL-12 p35 gene to lipopolysaccharide compared with interferon-gamma and CD40 ligation.

机译:与干扰素-γ和CD40连接相比,鼠IL-12 p35基因对脂多糖的差异反应。

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摘要

Expression of the heterodimeric cytokine interleukin-(IL-)12 is induced by pattern recognition receptors responding to microbial stimuli such as lipopolysaccharide (LPS) and products of the immune system such as interferon-gamma (IFN-gamma) and CD40L. The formation of bioactive IL-12 requires equimolar synthesis of p35 and p40 subunits. However, p35 expression limits the amount of IL-12 formed. Transcription of the gene for the p35 subunit of IL-12 initiates within the first exon, an alternate first exon (exon 1a), or second exon. Here we show that LPS and IFN-gamma/CD40 ligation increase the amount of total p35 mRNA in splenic adherent cells (SAC) to a similar extent. However, the exon 1 transcript was a smaller fraction of total p35 mRNA in IFN-gamma/CD40-stimulated cells than in unstimulated or LPS-stimulated cells. Despite comparable levels of total p35 mRNA, LPS-induced p35 exon 1 transcripts led to significantly more bioactive IL-12 from SAC than IFN-gamma/CD40-induced exon 1a/exon 2 transcripts as measured by ELISA. The data suggest that LPS-inducible p35 synthesis from exon 1 p35 transcripts leads to greater amount of bioactive IL-12 than IFN-gamma/CD40-induced p35 expression from alternate p35 exon 1a/exon 2 transcripts. Copyright 2001 Academic Press.
机译:异源二聚体细胞因子白介素-(IL-)12的表达是由对微生物刺激(例如脂多糖(LPS))和免疫系统产物(例如干扰素-γ(IFN-γ)和CD40L)产生响应的模式识别受体诱导的。具有生物活性的IL-12的形成需要p35和p40亚基的等摩尔合成。但是,p35表达限制了形成的IL-12的数量。 IL-12 p35亚基基因的转录起始于第一个外显子,另一个第一个外显子(外显子1a)或第二个外显子内。在这里,我们显示LPS和IFN-γ/ CD40的连接以相似的程度增加了脾黏附细胞(SAC)中总p35 mRNA的量。但是,与未刺激或LPS刺激的细胞相比,在IFN-γ/ CD40刺激的细胞中外显子1转录本占总p35 mRNA的比例较小。尽管总p35 mRNA的水平相当,但通过ELISA测定,LPS诱导的p35外显子1转录物比SAVIFN-γ/ CD40诱导的外显子1a /外显子2转录物产生的生物活性IL-12明显更高。数据表明,外源子1 p35转录本可诱导LPS诱导的p35合成导致比其他p35外显子1a /外显子2转录本中IFN-γ/ CD40诱导的p35表达量更大的生物活性IL-12。版权所有2001,学术出版社。

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