Effects of mesalamine on the hsp72 stress response in rat IEC-18 intestinal epithelial cells.
OBJECTIVE
Mesalamine has many effects and is commonly used for the treatment of inflammatory bowel diseases. Because sodium salicylate, a related compound, modulates the heat shock protein (hsp72) response in nonepithelial cells, the possibility that mesalamine confers cell protection by increasing intestinal epithelial hsp72 expression was 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 the threshold and time course of hsp72 thermal induction were determined.


RESULTS
Although mesalamine had no effects on the basal hsp72 expression or its thermal activation threshold in IEC-18 cells, it accelerated and augmented thermal induction of hsp72 within the first 2 hours of exposure. This was associated with a transient increase in heat shock factor-heat shock element binding and enhanced cellular protection against oxidant-induced injury. In contrast, both mesalamine and sodium salicylate have been shown to lower the thermal induction threshold but not to enhance the hsp72 response in HeLa cells.


CONCLUSIONS
Mesalamine augments thermal induction of the intestinal epithelial hsp72 expression in a manner that differs from that in nonintestinal epithelial cells. This effect is accompanied by increased cellular protection against oxidant injury.
Burress
G C
GC
Inflammatory Bowel Disease Research Center, Department of Medicine, University of Chicago, Illinois 60637, USA.
Musch
M W
MW
Jurivich
D A
DA
Welk
J
J
Chang
E B
EB
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects*; D019804:Mesalamine / Q000494:pharmacology*; D051381:Rats; D012980:Sodium Salicylate / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D019804:Mesalamine; D004247:DNA; D012980:Sodium Salicylate