Cutting edge: coordinate regulation of IFN regulatory factor-1 and the polymeric Ig receptor by proinflammatory cytokines.
Cutting edge: coordinate regulation of IFN regulatory factor-1 and the polymeric Ig receptor by proinflammatory cytokines.
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DOI：
10.4049/jimmunol.162.3.1232
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发表时间：
1999-02
影响因子：
4.4
通讯作者：
V. J. Blanch;J. Piskurich;C. Kaetzel
中科院分区：
文献类型：
--
作者：
V. J. Blanch;J. Piskurich;C. Kaetzel
多聚IgR（pIgR）介导IgA穿过粘膜和外分泌腺的上皮屏障的转胞吞作用。在HT-29人结肠癌细胞中，促炎细胞因子TNF-α、IFN-γ和IL-1上调pIgR的合成。我们以前报道过IFN-γ和TNF-α诱导HT-29细胞中转录因子IFN调节因子-1（IRF-1）的产生，并且IRF-1与PIGR基因外显子1中的元件结合。我们现在报道，HT-29细胞中IRF-1和pIgR mRNA水平受TNF-α、IFN-γ和IL-1 β的协同调节。此外，我们证明，在体内表达的pIgR mRNA的IRF-1缺陷小鼠的肠和肝脏中被大大抑制。我们的研究结果表明，IRF-1转录因子在PIGR基因的调控中发挥着重要作用，并提出了一种通过促炎细胞因子调控粘膜免疫系统中重要基因的模型。
The polymeric IgR (pIgR) mediates transcytosis of IgA across epithelial barriers of mucous membranes and exocrine glands. Synthesis of pIgR is up-regulated by the proinflammatory cytokines TNF-alpha, IFN-gamma, and IL-1 in HT-29 human colon carcinoma cells. We previously reported that IFN-gamma and TNF-alpha induce production of the transcription factor IFN regulatory factor-1 (IRF-1) in HT-29 cells and that IRF-1 binds to an element in exon 1 of the PIGR gene. We now report that levels of IRF-1 and pIgR mRNA are coordinately regulated in HT-29 cells by TNF-alpha, IFN-gamma, and IL-1beta. Furthermore, we demonstrate that in vivo expression of pIgR mRNA is greatly depressed in the intestine and liver of IRF-1-deficient mice. Our findings indicate a major role for the IRF-1 transcription factor in regulation of the PIGR gene and suggest a model for regulation of important genes in the mucosal immune system by proinflammatory cytokines.