Urayama S, Musch M W, Retsky J, Madonna M B, Straus D, Chang E B
Inflammatory Bowel Disease Research Center, University of Chicago, Chicago, Illinois 60637, USA.
J Clin Invest. 1998 Nov 15;102(10):1860-5. doi: 10.1172/JCI2235.
Although the therapeutic actions of glucocorticoids are largely attributed to their anti-inflammatory and immunosuppressive effects, they have been implicated in enhancing tissue and cellular protection. In this study, we demonstrate that dexamethasone significantly enhances viability of IEC-18 rat small intestinal cells against oxidant-induced stress in a dose-dependent fashion. This protective action is mediated by induction of hsp72, the major inducible heat shock protein in intestinal epithelial cells. Dexamethasone stimulates a time- and dose-dependent response in hsp72 protein expression that parallels its effects on cell viability. Furthermore, the induction of hsp72 is tissue dependent, as nonintestinal epithelioid HeLa cells show differential induction of hsp72 expression in response to the same dexamethasone treatment. Antisense hsp72 cDNA transfection of IEC-18 cells abolishes the dexamethasone-induced hsp72 response, without significantly affecting constitutive expression of its homologue, hsc73. Dexamethasone treatment also significantly induces hsp72 protein expression in rat intestinal mucosal cells in vivo. These data demonstrate that glucocorticoids protect intestinal epithelial cells against oxidant-induced stress by inducing hsp72.
尽管糖皮质激素的治疗作用主要归因于其抗炎和免疫抑制作用，但它们也被认为具有增强组织和细胞保护的作用。在本研究中，我们证明地塞米松能以剂量依赖的方式显著提高IEC-18大鼠小肠细胞在氧化剂诱导的应激下的活力。这种保护作用是由诱导hsp72介导的，hsp72是肠上皮细胞中主要的诱导型热休克蛋白。地塞米松刺激hsp72蛋白表达呈现时间和剂量依赖性反应，这与其对细胞活力的影响相似。此外，hsp72的诱导具有组织依赖性，因为非肠上皮样的HeLa细胞在相同的地塞米松处理下，hsp72表达的诱导情况有所不同。IEC-18细胞的反义hsp72 cDNA转染消除了地塞米松诱导的hsp72反应，而对其同源物hsc73的组成型表达没有显著影响。地塞米松处理在体内也能显著诱导大鼠肠黏膜细胞中hsp72蛋白的表达。这些数据表明，糖皮质激素通过诱导hsp72来保护肠上皮细胞免受氧化剂诱导的应激。
