Mesalamine promotes intestinal epithelial wound healing in vitro through a TGF-beta-independent mechanism.
OBJECTIVE
Treatment with 5-aminosalicylic acid (5-ASA) derivatives is one of the main principles in the therapy of uncomplicated mild to moderate inflammatory bowel diseases (IBD). The beneficial effect of 5-ASA in the treatment of IBD is attributed to its anti-inflammatory and anti-oxidant properties within the inflamed gut. The aim of this study was to investigate whether 5-ASA also modulates intestinal epithelial wound repair in vitro.


METHODS
The effects of 5-ASA on cell migration and proliferation, two key processes in mucosal healing, were studied in the non-transformed small-intestinal epithelial cell line IEC-6 using an in vitro wounding model and colorimetric MTT assays. Furthermore, the effects of 5-ASA on epithelial cell viability were determined by Trypan blue exclusion and flow cytometry-based cell cycle analysis.


RESULTS
Clinically relevant concentrations of 5-ASA caused a significant dose-dependent enhancement of epithelial cell migration and proliferation in vitro. An about 2-fold enhancement of intestinal epithelial cell proliferation and migration was observed for pharmacological doses of 100 microg/ml 5-ASA. Neutralizing antibodies against TGFbeta did not modulate 5-ASA effects on IEC-6 cell proliferation and migration, indicating that the effects of 5-ASA were TGFbeta independent. Trypan blue viability tests and cell cycle analysis did not reveal any toxic or apoptotic effects of pharmacological 5-ASA concentrations on IEC-6 cells.


CONCLUSIONS
5-ASA promotes the rapid re-establishment of mucosal integrity in vitro by enhancing epithelial restitution and proliferation, suggesting that 5-ASA in addition to the well-characterized effects on the intestinal inflammatory cascade may also directly stimulate epithelial wound healing.
Baumgart
Daniel C
DC
Department of Medicine, Division of Hepatology & Gastroenterology, Charité Medical Center-Virchow Hospital, Medical School of the Humboldt-University of Berlin, Germany.
Vierziger
Karin
K
Sturm
Andreas
A
Wiedenmann
Bertram
B
Dignass
Axel U
AU
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D017209:Apoptosis; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005434:Flow Cytometry; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D019804:Mesalamine / Q000627:therapeutic use*; D051381:Rats; D016212:Transforming Growth Factor beta / Q000502:physiology*; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology; D014947:Wounds and Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016212:Transforming Growth Factor beta; D019804:Mesalamine