Document Detail

Implication of TNF-related apoptosis-inducing ligand in inflammatory intestinal epithelial lesions.
MedLine Citation:
PMID:  16762619     Owner:  NLM     Status:  MEDLINE    
BACKGROUND & AIMS: Few data exist on the molecular events causing intestinal epithelial destruction during inflammatory processes, such as inflammatory bowel disease (IBD). In this work, we analyzed the potential implication of tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) in these inflammatory lesions. METHODS: TRAIL and TRAIL-receptor expression were analyzed in normal, inflammatory ileum/colon and human intestinal epithelial cell (IEC) lines (HIEC), Caco-2, and HT-29 using RNase protection assay, real-time and reverse-transcription polymerase chain reaction (RT-PCR), immunohistochemistry, and Western blot analysis. TRAIL-induced activation of NF-kappaB was determined by electrophoretic mobility shift assay. Caspase-recruitment domain (CARD)15 expression and interleukin-(IL)8 production were studied by RT-PCR and enzyme-linked immunosorbent assay. Apoptosis was monitored using Annexin-V/caspase-3 assays. RESULTS: Normal mature IEC expressed low TRAIL levels, whereas, in inflammatory lesions, TRAIL messenger RNA and protein were markedly up-regulated in IEC and lamina propria lymphocytes at levels comparable with trinitrobenzene sulfonic acid-induced colitis. Interferon-gamma and TNF-alpha potently induced TRAIL in IEC. In vitro analyses revealed a dual biologic effect of TRAIL on HIEC: Under noninflammatory conditions, TRAIL up-regulated via nuclear factor-kappaB CARD15 and IL-8, whereas, under inflammatory conditions, TRAIL became a potent inducer of apoptosis in HIEC, which was confirmed ex vivo using ileal organ cultures. TNF-alpha markedly increased the expression of the proapoptotic receptor TRAIL-R2. TRAIL-induced IEC apoptosis required a functional caspase cascade. CONCLUSIONS: TRAIL is a new inflammatory mediator implicated in the homeostasis of intestinal epithelial barrier functions. TRAIL is highly up-regulated in IEC in inflammatory ileum and colon. It may augment in an auto-/paracrine fashion the elimination of IEC via apoptosis.
Bernadette Begue; Harald Wajant; Jean-Christophe Bambou; Laurent Dubuquoy; Daniela Siegmund; Jean-François Beaulieu; Danielle Canioni; Dominique Berrebi; Nicole Brousse; Pierre Desreumaux; Jacques Schmitz; Michael J Lentze; Oliver Goulet; Nadine Cerf-Bensussan; Frank M Ruemmele
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Gastroenterology     Volume:  130     ISSN:  0016-5085     ISO Abbreviation:  Gastroenterology     Publication Date:  2006 Jun 
Date Detail:
Created Date:  2006-06-09     Completed Date:  2006-07-18     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0374630     Medline TA:  Gastroenterology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1962-74     Citation Subset:  AIM; IM    
INSERM U793, Faculté de Médecine Necker, Université Paris V, Paris, France.
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MeSH Terms
Apoptosis / genetics*
Apoptosis Regulatory Proteins / genetics*,  metabolism
Base Sequence
Blotting, Western
Cells, Cultured
Disease Models, Animal
Epithelial Cells / cytology*,  metabolism
Flow Cytometry
Gene Expression Regulation
Inflammation Mediators / metabolism*
Inflammatory Bowel Diseases / genetics,  pathology
Interleukin-8 / metabolism*
Membrane Glycoproteins / genetics*,  metabolism
Mice, Inbred BALB C
Molecular Sequence Data
Reference Values
Reverse Transcriptase Polymerase Chain Reaction
Sampling Studies
Sensitivity and Specificity
Statistics, Nonparametric
TNF-Related Apoptosis-Inducing Ligand
Tumor Necrosis Factor-alpha / genetics*,  metabolism
Reg. No./Substance:
0/Apoptosis Regulatory Proteins; 0/Inflammation Mediators; 0/Interleukin-8; 0/Membrane Glycoproteins; 0/TNF-Related Apoptosis-Inducing Ligand; 0/TNFSF10 protein, human; 0/Tnfsf10 protein, mouse; 0/Tumor Necrosis Factor-alpha

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