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Corticosteroids impair intestinal epithelial wound repair mechanisms in vitro
S Jung1, S Fehr, J Harder-d'Heureuse
1Dept. of Hepatology and Gastroenterology, University Clinic Charité-Campus Virchow Clinic, Berlin, Germany.
Background:
Despite enormous progress in the medical treatment of inflammatory bowel diseases (IBD), corticosteroids still represent the most effective drugs in the management of acute IBD. Unfortunately, surgical intervention under concomitant therapy with corticosteroids is often complicated by impaired intestinal wound healing. Our aim was to assess the effects of the corticosteroids prednisolone and budesonide on different aspects of intestinal epithelial wound healing in vitro to identify potential causes for impaired intestinal wound healing under corticosteroid therapy.
Methods:
The effects of both corticosteroids on intestinal epithelial cell function were studied in non-transformed small intestinal epithelial intestinal epithelial cell line IEC-6 cells and human colon cancer-derived HT-29 cells. Effects on epithelial migration were assessed using an in vitro wounding model. Effects on epithelial cell proliferation were assessed using colorimetric 3(4,5-dimethylthiazolyl-2)-2,5-diphenyl tetrazolium bromide (MTT) assays. Transforming Growth Factor beta (TGFbeta) mRNA and protein expression were determined by semi-quantitative RT-PCR and ELISA.
Results:
Prednisolone and budesonide caused a significant dose-dependent inhibition of intestinal epithelial cell migration and proliferation in IEC-6 and HT-29 cells. Both corticosteroids induced apoptosis of intestinal epithelial cells in a dose-dependent fashion. Neither corticosteroid modulated the expression of TGFbeta mRNA and the synthesis of TGFbeta peptide. However, both corticosteroids stimulated the bioactivation of latent TGFbeta peptide.
Conclusions:
Prednisolone and budesonide inhibit intestinal epithelial cell restitution and proliferation in vitro. Both processes play a key role in the rapid resealing of the mucosal barrier following intestinal injury. Thus, impaired intestinal epithelial wound healing under corticosteroid therapy in vivo may be caused by inhibition of intestinal epithelial cell restitution and proliferation.