Document Detail

IL-10 protects mouse intestinal epithelial cells from Fas-induced apoptosis via modulating Fas expression and altering caspase-8 and FLIP expression.
MedLine Citation:
PMID:  17030898     Owner:  NLM     Status:  MEDLINE    
We have previously shown that the absence of Fas/Fas ligand significantly reduced tissue damage and intestinal epithelial cell (IEC) apoptosis in an in vivo model of T cell-mediated enteropathy. This enteropathy was more severe in IL-10-deficient mice, and this was associated with increased serum levels of IFN-gamma and TNF-alpha and an increase in Fas expression on IECs. In this study, we investigated the potential of IL-10 to directly influence Fas expression and Fas-induced IEC apoptosis. Mouse intestinal epithelial cell lines MODE-K and IEC4.1 were cultured with IFN-gamma, TNF-alpha, or anti-Fas monoclonal antibody (mAb) in the presence or absence of IL-10. Fas expression and apoptosis were determined by FACScan analysis of phycoerythrin-anti-Fas mAb staining and annexin V staining, respectively. Treatment with a combination of IFN-gamma and TNF-alpha induced significant apoptosis. Anti-Fas mAb alone did not induce much apoptosis unless cells were pretreated with IFN-gamma and TNF-alpha. These IECs constitutively expressed low levels of Fas, which significantly increased by preincubation of the cells with IFN-gamma and TNF-alpha. Treatment with cytokine or cytokine plus anti-Fas mAb increased apoptosis, which correlated with a decreased Fas-associated death domain IL-1-converting enzyme-like inhibitory protein (FLIP) level, increased caspase-8 activity, and subsequently increased caspase-3 activity. IL-10 diminished both cytokine- and anti-Fas mAb-induced apoptosis, and this was correlated with decreased cytokine-induced Fas expression, increased FLIP, and decreased caspase-8 and caspase-3 activity. In conclusion, IL-10 modulated cytokine induction of Fas expression on IEC cell lines and regulated IEC susceptibility to TNF-alpha, IFN-gamma, and Fas-mediated apoptosis. These findings suggest that IL-10 directly modulates IEC responses to T cell-mediated apoptotic signals.
Mantej S Bharhani; Rajka Borojevic; Shibesh Basak; Edwin Ho; Pengfei Zhou; Kenneth Croitoru
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  American journal of physiology. Gastrointestinal and liver physiology     Volume:  291     ISSN:  0193-1857     ISO Abbreviation:  Am. J. Physiol. Gastrointest. Liver Physiol.     Publication Date:  2006 Nov 
Date Detail:
Created Date:  2006-10-10     Completed Date:  2006-11-24     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  100901227     Medline TA:  Am J Physiol Gastrointest Liver Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  G820-9     Citation Subset:  IM    
Intestinal Disease Research, Department of Medicine, McMaster University, Hamilton, ON, Canada.
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MeSH Terms
Annexin A5 / metabolism
Antibodies, Monoclonal / diagnostic use
Antigens, CD95 / biosynthesis,  genetics,  physiology*
Apoptosis / drug effects*
Blotting, Western
CASP8 and FADD-Like Apoptosis Regulating Protein / genetics*
Caspase 8 / biosynthesis*,  genetics
Cytokines / metabolism
Dose-Response Relationship, Drug
Electrophoresis, Polyacrylamide Gel
Epithelial Cells / drug effects*
Interferon-gamma / pharmacology
Interleukin-10 / pharmacology*
Intestinal Mucosa / cytology,  drug effects*
Mice, Inbred C3H
Tumor Necrosis Factor-alpha / pharmacology
Up-Regulation / drug effects
Reg. No./Substance:
0/Annexin A5; 0/Antibodies, Monoclonal; 0/Antigens, CD95; 0/CASP8 and FADD-Like Apoptosis Regulating Protein; 0/Cytokines; 0/Tumor Necrosis Factor-alpha; 130068-27-8/Interleukin-10; 82115-62-6/Interferon-gamma; EC 3.4.22.-/Caspase 8

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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