Document Detail

In vitro effects of dextran sulfate sodium on a Caco-2 cell line and plausible mechanisms for dextran sulfate sodium-induced colitis.
MedLine Citation:
PMID:  17089061     Owner:  NLM     Status:  MEDLINE    
Pathogenic mechanisms responsible for inflammatory bowel disease (IBD) are poorly understood. In an IBD animal model, the oral administration of polysaccharides such as dextran sulfate sodium (DSS) induces colitis, which exhibit several clinical and histological features for IBD. However, pathogenic factors in the development of colitis remain unclear. Therefore, we investigated possible mechanisms for DSS-induced colitis, and mainly focused on biological responses from an intestinal epithelial cell line, Caco-2. Cytotoxicity and cytokine release were measured using MTS assays and ELISA, respectively. The effect of DSS on the transepithelial electrical resistance (TEER) of Caco-2 cell monolayers was also evaluated. Cell cycle progression was estimated using antibodies directed against p53 and cdc-2 proteins. The generation of reactive oxygen species (ROS) was measured using a DCFH-DA method. Pyridylamino-DSS (PA-DSS) was used as a fluorometric label in order to investigate fluorescence-microscopically the location of DSS in Caco-2 cells. DSS induced cytotoxicity on Caco-2 cells at 5%. DSS also induced strong TEER decrease at 3%. DSS induced the weak release of IL-8, IL-6, and TGF-beta1. Remarkably DSS arrested Caco-2 cell cycle and reduced the intracellular generation of ROS. Under fluorescence microscopy, PA-DSS entered cells and bound to the nucleus, indicating this binding of DSS may be involved in the cell cycle arrest of Caco-2 cells. The cell cycle arrest and reduced intracellular generation of ROS may be involved during initiation or throughout the early stages of DSS-induced colitis.
Yoshio Araki; Hiroyuki Sugihara; Takanori Hattori
Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  Oncology reports     Volume:  16     ISSN:  1021-335X     ISO Abbreviation:  Oncol. Rep.     Publication Date:  2006 Dec 
Date Detail:
Created Date:  2006-11-07     Completed Date:  2006-12-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9422756     Medline TA:  Oncol Rep     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  1357-62     Citation Subset:  IM    
First Department of Pathology, Shiga University of Medical Science, Seta Tsukinowa, Otsu 520-2192, Shiga, Japan.
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MeSH Terms
Caco-2 Cells
Cell Cycle / drug effects
Cell Cycle Proteins / drug effects
Colitis / chemically induced*
Dextran Sulfate / toxicity*
Electric Impedance
Enzyme-Linked Immunosorbent Assay
Microscopy, Fluorescence
Reactive Oxygen Species / metabolism
Tumor Suppressor Protein p53 / drug effects
Reg. No./Substance:
0/Cell Cycle Proteins; 0/Reactive Oxygen Species; 0/Tumor Suppressor Protein p53; 9042-14-2/Dextran Sulfate

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