Burress G C, Musch M W, Jurivich D A, Welk J, Chang E B
Inflammatory Bowel Disease Research Center, Department of Medicine, University of Chicago, Illinois 60637, USA.
Gastroenterology. 1997 Nov;113(5):1474-9. doi: 10.1053/gast.1997.v113.pm9352849.
BACKGROUND & AIMS: 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.
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.
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.
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.
美沙拉嗪具有多种作用，常用于治疗炎症性肠病。由于相关化合物水杨酸钠可调节非上皮细胞中的热休克蛋白（hsp72）反应，因此研究了美沙拉嗪是否通过增加肠道上皮hsp72表达来提供细胞保护作用。
用0.3 - 3 mmol/L美沙拉嗪处理大鼠肠道IEC - 18细胞，并在39℃ - 42℃下热应激23分钟。测定美沙拉嗪对基础表达以及hsp72热诱导阈值和时间进程的影响。
虽然美沙拉嗪对IEC - 18细胞中的基础hsp72表达或其热激活阈值没有影响，但在暴露的前2小时内加速并增强了hsp72的热诱导。这与热休克因子 - 热休克元件结合的短暂增加以及增强细胞对氧化剂诱导损伤的保护作用有关。相比之下，美沙拉嗪和水杨酸钠都已被证明可降低热诱导阈值，但在HeLa细胞中不会增强hsp72反应。
美沙拉嗪以不同于非肠道上皮细胞的方式增强肠道上皮hsp72表达的热诱导。这种作用伴随着细胞对氧化损伤保护作用的增加。
