EFFECTS OF MESALAMINE ON THE HSP72 STRESS-RESPONSE IN RAT IEC-18 INTESTINAL EPITHELIAL-CELLS

Background & Aims: Mesalamine has many effects and is commonly used fo r the treatment of inflammatory bower diseases. Because sodium salicyl ate, a related compound, modulates the heat shock protein (hsp72) resp onse in nonepithelial cells, the possibility that mesalamine confers c ell protection by increasing intestinal epithelial hsp72 expression wa s examined. Methods: Rat intestinal IEC-18 cells were treated with 0.3 -3 mmol/L mesalamine and thermally stressed (39 degrees C-42 degrees C ) for 23 minutes. The effects of mesalamine on basal expression and th e threshold and time course of hsp72 thermal induction were determined . Results: Although mesalamine had no effects on the basal hsp72 expre ssion or its thermal activation threshold in IEC-18 cells, it accelera ted and augmented thermal induction of hsp72 within the first 2 hours of exposure. This was associated with a transient increase in heat sho ck factor-heat shock element binding and enhanced cellular protection against oxidant-induced injury. In contrast, both mesalamine and sodiu m salicylate have been shown to lower the thermal induction threshold but not to enhance the hsp72 response in HeLa cells. Conclusions: Mesa lamine augments thermal induction of the intestinal epithelial hsp72 e xpression in a manner that differs from that in nonintestinal epitheli al cells. This effect is accompanied by increased cellular protection against oxidant injury.