Interferon-gamma and tumor necrosis factor-alpha disrupt epithelial barrier function by altering lipid composition in membrane microdomains of tight junction

	Interferon-gamma and tumor necrosis factor-alpha disrupt epithelial barrier function by altering lipid composition in membrane microdomains of tight junction
	Li, Qiurong 1; Zhang, Qjang 1; Wang, Meng 1,3; Zhao, Sumin 2; Ma, Jian 1; Luo, Nan 1; Li, Ning 1; Li, Yousheng 1; Xu, Guowang 2; Li, Jieshou 1
刊名	clinical immunology
	2008
卷号	126 期号:1 页码:67-80
关键词	tight junction barrier function membrane microdomains fatty acid composition phospholipids tight junction proteins
通讯作者	黎介寿
产权排序	2;4
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.
WOS标题词	science & technology ; life sciences & biomedicine
类目[WOS]	immunology
研究领域[WOS]	immunology
关键词[WOS]	inflammatory-bowel-disease ; intestinal permeability ; crohns-disease ; proinflammatory cytokines ; tnf-alpha ; cells ; apoptosis ; proteins ; activation ; mechanisms
收录类别	SCI
原文出处	true
语种	英语
WOS记录号	WOS:000252416400007
公开日期	2010-11-30
内容类型	期刊论文
源URL	[http://159.226.238.44/handle/321008/99595]
专题	大连化学物理研究所_中国科学院大连化学物理研究所
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
推荐引用方式 GB/T 7714	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.
APA	Li, Qiurong.,Zhang, Qjang.,Wang, Meng.,Zhao, Sumin.,Ma, Jian.,...&Li, Jieshou.(2008).Interferon-gamma and tumor necrosis factor-alpha disrupt epithelial barrier function by altering lipid composition in membrane microdomains of tight junction.clinical immunology,126(1),67-80.
MLA	Li, Qiurong,et al."Interferon-gamma and tumor necrosis factor-alpha disrupt epithelial barrier function by altering lipid composition in membrane microdomains of tight junction".clinical immunology 126.1(2008):67-80.