Acute stress-induced colonic tissue HSP70 expression requires commensal bacterial components and intrinsic glucocorticoid
Acute stress-induced colonic tissue HSP70 expression requires commensal bacterial components and intrinsic glucocorticoid
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DOI：
10.1016/j.bbi.2008.07.013
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发表时间：
2009-01
期刊：
影响因子：
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通讯作者：
Kaori Matsuo;Xiumin Zhang;Y. Ono;R. Nagatomi
中科院分区：
文献类型：
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作者：
Kaori Matsuo;Xiumin Zhang;Y. Ono;R. Nagatomi
诱导热休克蛋白（HSPs）对应激细胞具有保护作用。体内抑制等物理应激源可诱导结肠组织产生热休克蛋白，但其诱导机制尚不清楚。由于共生菌支持结肠上皮HSP70的基础表达，我们假设应激反应可能增强共生菌与结肠组织的相互作用。抑制C57BL/6小鼠2h可有效诱导结肠上皮HSP70表达。RU486阻断应激诱导的糖皮质激素或抗生素消除共生菌均可单独消除抑制诱导的HSP70增强。口服脂多糖可恢复抑制诱导的HSP70升高。由于TLR4在上皮表面缺失表达，并且仅限于固有层和外肌层，因此我们研究了LPS如何到达固有层。在结肠内给药的Alexa-LPS仅在受限小鼠的固有层中检测到。调节腔内物质通过上皮的紧密连接成分ZO-1的表达在抑制后降低，但RU486使其表达逆转。综上所述，应激诱导的HSP70在受抑制的结肠上皮细胞中的诱导需要应激诱导的糖皮质激素和腔内共生菌的共同作用，其中LPS的作用显著。糖皮质激素依赖性的上皮紧密连接完整性衰减可能促进LPS进入固有层，而已知HSP70诱导所需的TLR4在固有层大量表达。结肠对应激源的保护涉及一般应激反应和腔内环境的复杂调节已被证明。
Induction of heat shock protein (HSPs) has a protective effect in cells under stress. Physical stressors, such as restraint, induce HSPs in colonic tissue in vivo, but the mechanism of HSP induction is not yet clear. Because commensal bacteria support basal expression of colon epithelial HSP70, we postulated that stress responses may enhance the interaction of commensal bacteria and the colonic tissue. Restraining C57BL/6 mice for 2h effectively induced HSP70 in colonic epithelia. Both blockade of stress-induced glucocorticoid by RU486 or elimination of commensal bacteria by antibiotics independently abrogated restraint-induced HSP70 augmentation. Oral administration of LPS to commensal-depleted mice restored restraint-induced HSP70 augmentation. Because TLR4 expression was absent from the epithelial surface, and was limited to lamina propria and muscularis externa, we examined how LPS reaches the lamina propria. Alexa-LPS administered in the colonic lumen was only detected in the lamina propria of the restrained mice. Expression of the tight junction component ZO-1 in the epithelia, which regulates the passage of luminal substances through the epithelia, was reduced after restraint, but reversed by RU486. In conclusion, HSP70 induction in colonic epithelial cells under restraint requires both stress-induced glucocorticoid and luminal commensal bacteria, and LPS plays a significant role. Glucocorticoid-dependent attenuation of epithelial tight junction integrity may facilitate the access of LPS into the lamina propria, where TLR4, known to be required for HSP70 induction, is abundantly expressed. Sophisticated regulation of colonic protection against stressors involving the general stress response and the luminal environment has been demonstrated.