Overexpression of a 60-kDa heat shock protein enhances cytoprotective function of small intestinal epithelial cells

Aims With the advancement of small intestinal (double balloon and capsule) endoscopy technology, incidence of small intestinal lesion caused by nonsteroidal anti-inflammatory drugs (NSAIDs) has been known to be high However, therapy for small intestinal mucosal lesion has not yet been developed Previous studies have shown that heat shock proteins (HSPs) are involved in cytoprotection mediated by their function as a molecular chaperone In this study, we examined the effect of HSP60 or HSP70 overexpression on hydrogen peroxide-induced (H2O2) or indomethacin-induced cell damage in the small intestinal epithelial cells Main methods cDNA of human HSP60 or HSP70 was transfected to rat small intestinal (IEC-6) cells, and HSP60- or HSP70-overexpressing cells were cloned IEC-6 cells transfected with vector only were used as control cells These cells were treated with H2O2 (0-0 14 mM) or indomethacin (0-25 mM) The cell viability was determined by MIT-assay. Cell necrosis was evaluated by LDH-release assay Furthei, apoptosis was evaluated by caspases-3/7 activity and TUNEL assay Key findings Cell viability after H2O2 or indomethacin treatment was significantly higher in HSP60-overexpiessing cells compared with that in control cells and HSP60-overexpressing cells Apoptotic cells were also reduced in HSP60-overexpressing Conclusion These results indicate that HSP60 plays an important role in protecting small intestinal mucosal cells from H2O2-induced or indomethacin-induced cell injury HSP70-overexpressing cells did not show anti-apoptotic ability Significance These findings possibly suggest that function of each HSP is different in the small intestine Therefore, for the therapy of small intestinal mucosal lesion. HSP60-induction therapy could be a new therapeutic strategy (C) 2010 Elsevier Inc All rights reserved.