Document Detail

Intestinal epithelial cells with impaired autophagy lose their adhesive capacity in the presence of TNF-α.
MedLine Citation:
PMID:  22466076     Owner:  NLM     Status:  MEDLINE    
BACKGROUND AND OBJECTIVES: Genome-wide association studies have revealed a link between autophagy-related (ATG) genes and susceptibility to Crohn's disease. This suggests underlying involvement of autophagy impairment in the pathogenesis of Crohn's disease. This study was performed to investigate the pathophysiological importance of autophagy impairment in intestinal epithelial cells exposed to TNF-α.
METHODS: Human colonic epithelial cells (HT-29) and rat small intestinal epithelial cells (IEC-18) were used. Formation of phosphatidylethanolamine-conjugated microtubule-associated protein light chain 3 (LC3-II) was monitored as a marker of autophagy. Autophagy was inhibited using 3-methyladenine or short interfering RNA targeting ATG5 and ATG16L1.
RESULTS: TNF-α treatment elicited a significant dose-dependent increase in LC3-II protein levels, thus autophagy is induced in the presence of TNF-α. Combined autophagy inhibition and TNF-α treatment induced a marked increase in the number of detached cells and a decrease in activated integrin β1 protein levels. Trypan blue staining indicated 70-80 % of the detached cells were alive, suggesting that these cells became detached not because they were killed but because of dysfunction of cellular adhesion.
CONCLUSIONS: This is the first study indicating that intestinal epithelial cells with impaired autophagy lose their adhesive capacity in the presence of TNF-α. These observations indicate that impairment of autophagy leads to disruption of the intestinal epithelial cell layers in TNF-α-rich environments.
Masaya Saito; Tatsuro Katsuno; Tomoo Nakagawa; Toru Sato; Yoshiko Noguchi; Sayuri Sazuka; Keiko Saito; Makoto Arai; Koutaro Yokote; Osamu Yokosuka
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Publication Detail:
Type:  Journal Article     Date:  2012-03-31
Journal Detail:
Title:  Digestive diseases and sciences     Volume:  57     ISSN:  1573-2568     ISO Abbreviation:  Dig. Dis. Sci.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-07-26     Completed Date:  2012-10-16     Revised Date:  2013-01-30    
Medline Journal Info:
Nlm Unique ID:  7902782     Medline TA:  Dig Dis Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2022-30     Citation Subset:  AIM; IM    
Department of Medicine and Clinical Oncology (K1), Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-shi 260-8670, Japan.
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MeSH Terms
Antigens, CD29 / metabolism
Cell Adhesion
Crohn Disease / etiology
Epithelial Cells / cytology
GTP-Binding Proteins / metabolism
HT29 Cells
Intestinal Mucosa / cytology,  physiology*
Tumor Necrosis Factor-alpha / physiology*
Reg. No./Substance:
0/Antigens, CD29; 0/Tumor Necrosis Factor-alpha; EC 3.6.1.-/Atg16L1 protein, rat; EC 3.6.1.-/GTP-Binding Proteins

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

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