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题名: Interferon-gamma and tumor necrosis factor-alpha disrupt epithelial barrier function by altering lipid composition in membrane microdomains of tight junction
作者: Li, Qiurong1;  Zhang, Qjang1;  Wang, Meng1, 3;  Zhao, Sumin2;  Ma, Jian1;  Luo, Nan1;  Li, Ning1;  Li, Yousheng1;  Xu, Guowang2;  Li, Jieshou1
通讯作者: 黎介寿
关键词: tight junction ;  barrier function ;  membrane microdomains ;  fatty acid composition ;  phospholipids ;  tight junction proteins
刊名: CLINICAL IMMUNOLOGY
发表日期: 2008
DOI: 10.1016/j.clim.2007.08.017
卷: 126, 期:1, 页:67-80
收录类别: SCI
文章类型: Article
部门归属: 18
项目归属: 1808
产权排名: 2;4
WOS标题词: Science & Technology ;  Life Sciences & Biomedicine
类目[WOS]: Immunology
研究领域[WOS]: Immunology
英文摘要: Tight junctions (TJs) are specialized membrane microdomains of plasma membrane and play an important role in barrier function. IFN-gamma and TNF-alpha have been implicated in intestinal barrier dysfunction. In the present study, we analyzed the effect of IFN-gamma and TNF-alpha on epithelial barrier function and determined the contribution of apoptosis to this process using T84 cells, a model intestinal epithelial cell line. We found that TNF-alpha and IFN-gamma synergistically affected the epithelial barrier and disrupted the structure of TJs. We demonstrated for the first time that treatment with TNF-alpha and IFN-gamma changed lipid composition and fatty acyl substitutions of phospholipids in membrane microdomains of TJs. Alterations of lipid environment affected TJs barrier function and partly removed flotillin-1 and displaced occludin from membrane microdomains of TJs to detergent-soluble fractions. The distribution of claudin isoforms was unaffected by TNF-alpha and IFN-gamma treatment. These findings indicated the interaction between inflammatory cytokines and alterations of lipid composition in membrane microdomains of TJs in the inflammatory processes. The apoptosis inhibitor did not prevent cytokine-induced decrease in TER and increase in permeability to FITC-dextran. Our results suggest that the cytokines directly influence TJ function and modulate both the membrane microdomain localization of TJ proteins and lipid composition of TJs. The effects of proinflammatory cytokines on TJ structure and function provide a mechanism in the pathophysiology of Crohn's disease (CD). Understanding the intracellular mechanisms involved could be important in devising future therapeutic strategies to induce retightening of the leaky TJ barrier. (C) 2007 Elsevier Inc. All rights reserved.
关键词[WOS]: INFLAMMATORY-BOWEL-DISEASE ;  INTESTINAL PERMEABILITY ;  CROHNS-DISEASE ;  PROINFLAMMATORY CYTOKINES ;  TNF-ALPHA ;  CELLS ;  APOPTOSIS ;  PROTEINS ;  ACTIVATION ;  MECHANISMS
语种: 英语
原文出处: 查看原文
WOS记录号: WOS:000252416400007
Citation statistics: 
内容类型: 期刊论文
URI标识: http://cas-ir.dicp.ac.cn/handle/321008/99595
Appears in Collections:中国科学院大连化学物理研究所_期刊论文

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作者单位: 1.Jinling Hosp, Inst Gen Surg, Nanjing 210002, Peoples R China
2.Chinese Acad Sci, Inst Chem Phys, Natl Chromatog Res & Anal Ctr, Dalian 116011, Peoples R China
3.Nanjing Univ, Sch Med, Nanjing 210093, Peoples R China

Recommended Citation:
Li, Qiurong,Zhang, Qjang,Wang, Meng,et al. Interferon-gamma and tumor necrosis factor-alpha disrupt epithelial barrier function by altering lipid composition in membrane microdomains of tight junction[J]. CLINICAL IMMUNOLOGY,2008,126(1):67-80.
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