Kim J M, Lee J Y, Yoon Y M, Oh Y-K, Youn J, Kim Y-J
Department of Microbiology and Institute of Biomedical Science, Hanyang University College of Medicine, Seoul, Korea.
Scand J Immunol. 2006 Jun;63(6):453-60. doi: 10.1111/j.1365-3083.2006.001756.x.
Intestinal epithelial cells are known to upregulate the expression of several chemokines in response to stimulation with bacterial toxin. However, the cellular mechanisms of Clostridium difficile toxin A-induced mucosal inflammation have not yet been fully elucidated. In this study, we investigated whether nuclear factor-kappa B (NF-kappaB) could regulate chemokine expression in intestinal epithelial cells. Toxin A increased the levels of NF-kappaB complexes containing p65/p50 heterodimers and p65/p65 homodimers. Concurrently, toxin A decreased the levels of IkappaBalpha. Toxin A stimulation also increased the signals of phosphorylated IkappaB kinase (IKK)alpha/beta and NF-kappaB-inducing kinase (NIK). In the toxin A-stimulated HT-29 cells, the suppression of IKK or NIK inhibited the upregulation of downstream target genes of NF-kappaB such as IL-8 and monocyte-chemotactic protein (MCP)-1 and similarly, inhibition of NF-kappaB also downregulated the expression of IL-8, growth-related oncogene-alpha, and MCP-1. These results suggest that NF-kappaB signalling events may be involved in the inflammatory responses to toxin A produced by toxigenic C. difficile.
已知肠道上皮细胞在受到细菌毒素刺激时会上调几种趋化因子的表达。然而，艰难梭菌毒素A诱导的黏膜炎症的细胞机制尚未完全阐明。在本研究中，我们调查了核因子-κB（NF-κB）是否能调节肠道上皮细胞中趋化因子的表达。毒素A增加了含有p65/p50异二聚体和p65/p65同二聚体的NF-κB复合物的水平。同时，毒素A降低了IκBα的水平。毒素A刺激还增加了磷酸化IκB激酶（IKK）α/β和NF-κB诱导激酶（NIK）的信号。在毒素A刺激的HT-29细胞中，IKK或NIK的抑制抑制了NF-κB下游靶基因如IL-8和单核细胞趋化蛋白（MCP）-1的上调，同样，NF-κB的抑制也下调了IL-8、生长相关癌基因-α和MCP-1的表达。这些结果表明，NF-κB信号事件可能参与了对产毒艰难梭菌产生的毒素A的炎症反应。
