Title: Transcription profiling of rat intestinal epithelial IEC-6 cells treated with non-steroidal anti-inflammatory agents to investigate gastrointestinal toxicity of NSAIDs
Organism(s): Rattus norvegicus
Description: IEC-6 cells were incubated with indomethacin, NS-398, or SC-560 for 72 hours. [original description: Non-steroidal anti-inflammatory drugs (NSAIDs) are used extensively as therapeutic agents, despite their well-documented gastrointestinal (GI) toxicity. Presently, the mechanisms responsible for NSAID-associated GI damage are incompletely understood. In this study, we used microarray analysis to generate a novel hypothesis about cellular mechanisms that underlie the GI toxicity of NSAIDs. Monolayers of intestinal epithelial; cells (IEC-6) were treated with NSAIDs that either [inhibit] (indomethacin, NS-398) or lack (SC-560) inhibitory effects on intestinal epithelial cell migration. Bioinformatic analysis of array data suggested that NSAIDs with adverse GI effects either decrease the gene expression of the calpains or increase the gene expression of the endogenous calpain inhibitor calpastatin. Calpains have been shown previously to modulate the migration of a variety of cells in different physiological contexts. Our experimental results suggest that the altered expression of calpain genes may contribute to the adverse effects of NSAIDs on intestinal; epithelial restitution. Microarray analysis has generated the novel hypothesis that the GI toxicity of NSAIDs may be attributed in part to drug-induced changes in the expression and activity of calpains. Experiment Overall Design: Monolayers of intestinal epithelial cells (IEC-6) were treated with NSAIDs that either exhibit (indomethacin, NS-398) or lack (SC-560) inhibitory effects on intestinal epithelial cell migration. Samples were then pooled to obtain sufficient material for gene array analysis. The pooled samples were used to hybridize 4 gene array chips for each biological sample.]
Design(s): unknown_experiment_design_type, transcription profiling by array
Publication(s): Raveendran NN, Silver K, Freeman LC, Narvaez D, Weng K, Ganta S, Lillich JD.
Drug-induced alterations to gene and protein expression in intestinal epithelial cell 6 cells suggest a role for calpains in the gastrointestinal toxicity of nonsteroidal anti-inflammatory agents. PubMed:18281595

Sample attribute(s):
NSAID concentration
3 recorded
0 micromolar 1 micromolar 100 micromolar
Material Type
3 recorded
synthetic_RNA organism_part total_RNA
4 recorded
vehicle control condition SC-560 indometacin NS-398
cell line
1 recorded
IEC-6 cell
1 recorded
1 recorded
Rattus norvegicus
Contact(s): Nithya Raveendran
Release Date: 3/27/2009
Submission Date:
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Assay Downloads
transcription profiling using DNA microarray
14 assays