Suppr超能文献

上皮细胞 NF-κB 通过改变 T 细胞激活后紧密连接蛋白的组成来增强跨黏膜液体运动。

Epithelial NF-kappaB enhances transmucosal fluid movement by altering tight junction protein composition after T cell activation.

机构信息

Division of Gastroenterology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.

出版信息

Am J Pathol. 2010 Jan;176(1):158-67. doi: 10.2353/ajpath.2010.090548. Epub 2009 Dec 11.

Abstract

In inflammatory bowel disease (IBD), aberrant activation of innate and adaptive immune responses enhances mucosal permeability through mechanisms not completely understood. To examine the role of epithelial nuclear factor (NF-kappaB) in IBD-induced enhanced permeability, epithelial-specific IkappaBalpha mutant (NF-kappaB super repressor) transgenic (TG) mice were generated. NF-kB activation was inhibited in TG mice, relative to wild-type mice, following T cell-mediated immune cell activation using an anti-CD3 monoclonal antibody. Furthermore, epithelial NF-kappaB super repressor protein inhibited diarrhea and blocked changes in transepithelial resistance and transmucosal flux of alexa350 (0.35 kDa) and dextran3000 (3 kDa). In vivo perfusion loop studies in TG mice revealed reversed net water secretion and reduced lumenal flux of different molecular probes (bovine serum albumin, alexa350, and dextran3000). Cell-imaging and immunoblotting of low-density, detergent-insoluble membrane fractions confirmed that tight junction proteins (occludin, claudin-1 and zona occludens-1) are internalized through an NF-kappaB-dependent pathway. Taken together, these data suggest that IBD-associated diarrhea results from NF-kappaB-mediated tight junction protein internalization and increased paracellular permeability. Thus, reduction of epithelial NF-kappaB activation in IBD may repair defects in epithelial barrier function, reduce diarrhea, and limit protein (eg, serum albumin) losses. Epithelial NF-kappaB activation induced by mucosal T cells, therefore, actively plays a role in opening paracellular spaces to promote transmucosal fluid effux into the intestinal lumen.

摘要

在炎症性肠病(IBD)中,先天和适应性免疫反应的异常激活通过尚未完全理解的机制增强了黏膜通透性。为了研究上皮核因子(NF-κB)在 IBD 诱导的通透性增强中的作用,生成了上皮特异性 IkappaBalpha 突变体(NF-κB 超级抑制剂)转基因(TG)小鼠。与野生型小鼠相比,在用抗 CD3 单克隆抗体介导的免疫细胞激活后,TG 小鼠中的 NF-κB 激活受到抑制。此外,上皮 NF-κB 超级抑制剂蛋白抑制腹泻,并阻止了跨上皮电阻和 Alexa350(0.35 kDa)和右旋糖酐 3000(3 kDa)的跨粘膜通量的变化。在 TG 小鼠的体内灌注环研究中,发现净水分泌逆转和不同分子探针(牛血清白蛋白、Alexa350 和右旋糖酐 3000)的腔内腔通量减少。低密度、去垢剂不可溶膜部分的细胞成像和免疫印迹证实,紧密连接蛋白(occludin、claudin-1 和 zona occludens-1)通过 NF-κB 依赖性途径内化。总之,这些数据表明,IBD 相关的腹泻是由 NF-κB 介导的紧密连接蛋白内化和增加的细胞旁通透性引起的。因此,在 IBD 中减少上皮 NF-κB 激活可能会修复上皮屏障功能的缺陷,减少腹泻,并限制蛋白质(例如血清白蛋白)的损失。因此,黏膜 T 细胞诱导的上皮 NF-κB 激活积极发挥作用,打开细胞旁间隙,促进跨粘膜液体流出肠腔。

相似文献

1
Epithelial NF-kappaB enhances transmucosal fluid movement by altering tight junction protein composition after T cell activation.
Am J Pathol. 2010 Jan;176(1):158-67. doi: 10.2353/ajpath.2010.090548. Epub 2009 Dec 11.
4
Interleukin-18 facilitates neutrophil transmigration via myosin light chain kinase-dependent disruption of occludin, without altering epithelial permeability.
Am J Physiol Gastrointest Liver Physiol. 2012 Feb 1;302(3):G343-51. doi: 10.1152/ajpgi.00202.2011. Epub 2011 Dec 1.
7
IL-1beta causes an increase in intestinal epithelial tight junction permeability.
J Immunol. 2007 Apr 1;178(7):4641-9. doi: 10.4049/jimmunol.178.7.4641.
8
Mechanism of interferon-gamma-induced increase in T84 intestinal epithelial tight junction.
J Interferon Cytokine Res. 2009 Jan;29(1):45-54. doi: 10.1089/jir.2008.0128.
10

引用本文的文献

6
Redox and Metabolic Regulation of Intestinal Barrier Function and Associated Disorders.
Int J Mol Sci. 2022 Nov 21;23(22):14463. doi: 10.3390/ijms232214463.
8
High-fat diet and alcohol induced-mice could cause colonic injury through molecular mechanisms of endogenous toxins.
Toxicol Res (Camb). 2022 Jul 30;11(4):696-706. doi: 10.1093/toxres/tfac025. eCollection 2022 Aug.
9
10
Dietary Oxidative Distress: A Review of Nutritional Challenges as Models for Poultry, Swine and Fish.
Antioxidants (Basel). 2021 Mar 27;10(4):525. doi: 10.3390/antiox10040525.

本文引用的文献

1
Mechanism of cytokine modulation of epithelial tight junction barrier.
Front Biosci (Landmark Ed). 2009 Jan 1;14(7):2765-78. doi: 10.2741/3413.
2
Mechanism of interferon-gamma-induced increase in T84 intestinal epithelial tight junction.
J Interferon Cytokine Res. 2009 Jan;29(1):45-54. doi: 10.1089/jir.2008.0128.
3
NF-kappaB in inflammatory bowel disease.
J Intern Med. 2008 Jun;263(6):591-6. doi: 10.1111/j.1365-2796.2008.01953.x.
5
Transmembrane proteins of tight junctions.
Biochim Biophys Acta. 2008 Mar;1778(3):588-600. doi: 10.1016/j.bbamem.2007.08.017. Epub 2007 Sep 4.
6
Epithelial NEMO links innate immunity to chronic intestinal inflammation.
Nature. 2007 Mar 29;446(7135):557-61. doi: 10.1038/nature05698. Epub 2007 Mar 14.
7
Epithelial-cell-intrinsic IKK-beta expression regulates intestinal immune homeostasis.
Nature. 2007 Mar 29;446(7135):552-6. doi: 10.1038/nature05590. Epub 2007 Feb 25.
9
Cytokines, NF-kappaB, microenvironment, intestinal inflammation and cancer.
Cancer Treat Res. 2006;130:67-87. doi: 10.1007/0-387-26283-0_3.
10
Molecular mechanism of tumor necrosis factor-alpha modulation of intestinal epithelial tight junction barrier.
Am J Physiol Gastrointest Liver Physiol. 2006 Mar;290(3):G496-504. doi: 10.1152/ajpgi.00318.2005.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验