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首页> 外文期刊>Clinical and diagnostic laboratory immunology >NF-κB Is Involved in Regulation of CD40 Ligand Expression on Mycobacterium bovis Bacillus Calmette-Guérin-Activated Human T Cells
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NF-κB Is Involved in Regulation of CD40 Ligand Expression on Mycobacterium bovis Bacillus Calmette-Guérin-Activated Human T Cells

机译：NF-κB参与牛分枝杆菌卡介苗激活人T细胞的CD40配体表达调控。

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Interaction between CD40L (CD154) on activated T cells and its receptor CD40 on antigen-presenting cells has been reported to be important in the resolution of infection by mycobacteria. However, the mechanism(s) by which Mycobacterium bovis bacillus Calmette-Guérin (BCG) up-regulates membrane expression of CD40L molecules is poorly understood. This study was done to investigate the role of the nuclear factor κB (NF-κB) signaling pathway in the regulation of CD40L expression in human CD4+ T cells stimulated with BCG. Specific pharmacologic inhibition of the NF-κB pathway revealed that this signaling cascade was required in the regulation of CD40L expression on the surface of BCG-activated CD4+ T cells. These results were further supported by the fact that treatment of BCG-activated CD4+ T cells with these pharmacological inhibitors significantly down-regulated CD40L mRNA. In this study, inhibitor κBα (IκBα) and IκBβ protein production was not affected by the chemical protease inhibitors and, more importantly, BCG led to the rapid but transient induction of NF-κB activity. Our results also indicated that CD40L expression on BCG-activated CD4+ T cells resulted from transcriptional up-regulation of the CD40L gene by a mechanism which is independent of de novo protein synthesis. Interestingly, BCG-induced activation of NF-κB and the increased CD40L cell surface expression were blocked by the protein kinase C (PKC) inhibitors 1-[5-isoquinolinesulfonyl]-2-methylpiperazine and salicylate, both of which block phosphorylation of IκB. Moreover, rottlerin a Ca2+-independent PKC isoform inhibitor, significantly down-regulated CD40L mRNA in BCG-activated CD4+ T cells. These data strongly suggest that CD40L expression by BCG-activated CD4+ T cells is regulated via the PKC pathway and by NF-κB DNA binding activity.
机译：据报道，活化的T细胞上的CD40L（CD154）与抗原呈递细胞上的CD40L受体之间的相互作用在分枝杆菌感染的消退中很重要。但是，人们对牛分枝杆菌卡介菌（BCG）上调CD40L分子膜表达的机制了解甚少。本研究旨在探讨核因子κB（NF-κB）信号通路在BCG刺激的人CD4 + T细胞中调节CD40L表达的作用。 NF-κB途径的特异性药理抑制作用表明，该信号级联反应是调节BCG活化的CD4 + T细胞表面CD40L表达所必需的。用这些药理抑制剂处理BCG激活的CD4 + T细胞可显着下调CD40L mRNA，这一事实进一步支持了这些结果。在这项研究中，抑制剂κBα（IκBα）和IκBβ蛋白的产生不受化学蛋白酶抑制剂的影响，更重要的是，卡介苗可快速但短暂地诱导NF-κB活性。我们的结果还表明，BCG激活的CD4 + T细胞上CD40L的表达是由CD40L基因的转录上调所致，其机制与新生蛋白质合成无关。有趣的是，BCG诱导的NF-κB活化和CD40L细胞表面表达的增加被蛋白激酶C（PKC）抑制剂1- [5-异喹啉磺酰基] -2-甲基哌嗪和水杨酸盐阻断，两者均阻断了IκB的磷酸化。此外，rottlerin是一种不依赖Ca 2 + 的PKC亚型抑制剂，在BCG激活的CD4 + T细胞中显着下调了CD40L mRNA。这些数据强烈表明，BCG激活的CD4 + T细胞的CD40L表达是通过PKC途径和NF-κBDNA结合活性来调节的。

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