Prolonged NF-κB Activation by a Macrophage Inhibitory Cytokine 1-Linked Signal in Enteropathogenic Escherichia coli-Infected Epithelial Cells
Prolonged NF-κB Activation by a Macrophage Inhibitory Cytokine 1-Linked Signal in Enteropathogenic Escherichia coli-Infected Epithelial Cells
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DOI：
10.1128/iai.00162-13
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发表时间：
2013-06-01
影响因子：
3.1
通讯作者：
Moon, Yuseok
中科院分区：
文献类型：
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作者：
Choi, Hye Jin;Kim, Juil;Moon, Yuseok
肠上皮核因子κ B （nf - κ B）的激活在应对各种肠道损伤（包括与粘膜相关的病原体）时发挥有害和有益的功能。肠道致病性大肠杆菌（EPEC）的胃肠道感染会导致上皮完整性严重损伤并导致水样腹泻。本研究旨在通过NF-kappa B激活研究持续EPEC感染的延长上皮反应。EPEC感染导致小鼠肠上皮细胞内NF-kappa B信号在体内和体外持续激活，这与III型分泌系统呈正相关，而早期NF-kappa B受到调节。此外，延长的NF-kappa B激活被发现是巨噬细胞抑制性细胞因子1 （MIC-1）介导的信号激活的一部分，这是NF-kappa B信号传导与感染相关上皮应激之间的新联系。EPEC感染诱导转化生长因子β (tgf - β)超家族成员MIC-1的基因表达，然后激活tgf - β活化激酶1，从而导致NF-kappa B活化。在功能上，epec诱导的MIC-1和NF-kappa B信号通过增强细胞周期蛋白D1 （NF-kappa B的靶标）的表达来介导上皮细胞的存活。总之，本研究的结果表明，MIC-1是延长NF-kappa B激活的介质，这对于维持肠道上皮在感染诱导损伤反应中的完整性至关重要。
Intestinal epithelial activation of nuclear factor kappa B (NF-kappa B) exerts both detrimental and beneficial functions in response to various luminal insults, including ones associated with mucosa-associated pathogens. Gastrointestinal infection with enteropathogenic Escherichia coli (EPEC) causes severe injuries in epithelial integrity and leads to watery diarrhea. The present study was conducted to investigate the prolonged epithelial responses to persistent EPEC infection via NF-kappa B activation. EPEC infection led to sustained activation of NF-kappa B signal in mouse intestinal epithelial cells in vivo and in vitro, which was positively associated with a type III secretion system, whereas early NF-kappa B is regulated. Moreover, prolonged NF-kappa B activation was found to be a part of macrophage inhibitory cytokine 1 (MIC-1)-mediated signaling activation, a novel link between NF-kappa B signaling and infection-associated epithelial stress. EPEC infection induced gene expression of MIC-1, a member of the transforming growth factor beta (TGF-beta) superfamily, which then activated TGF-beta-activated kinase 1 and consequently led to NF-kappa B activation. Functionally, both EPEC-induced MIC-1 and NF-kappa B signaling mediated epithelial survival by enhancing the expression of cyclin D1, a target of NF-kappa B. In summary, the results of the present study suggest that MIC-1 serves as a mediator of prolonged NF-kappa B activation, which is critical in maintaining gut epithelial integrity in response to infection-induced injuries.