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首页> 外文期刊>American Journal of Physiology >Physiologically relevant increase in temperature causes an increase in intestinal epithelial tight junction permeability.
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Physiologically relevant increase in temperature causes an increase in intestinal epithelial tight junction permeability.

机译：生理上相关的温度升高导致肠上皮紧密连接通透性增加。

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The effects of physiologically relevant increase in temperature (37-41 degrees C) on intestinal epithelial tight junction (TJ) barrier have not been previously studied. Additionally, the role of heat-shock proteins (HSPs) in the regulation of intestinal TJ barrier during heat stress remains unknown. Because heat-induced disturbance of intestinal TJ barrier could lead to endotoxemia and bacterial translocation during physiological thermal stress, the purpose of this study was to investigate the effects of modest, physiologically relevant increases in temperature (37-41 degrees C) on intestinal epithelial TJ barrier and to examine the protective role of HSPs on intestinal TJ barrier. Filter-grown Caco-2 intestinal epithelial cells were used as an in vitro intestinal epithelial model system to assess the effects of heat exposure on intestinal TJ barrier. Exposure of filter-grown Caco-2 monolayers to modest increases in temperatures (37-41 degrees C) resulted in a significant time- and temperature-dependent increases in Caco-2 TJ permeability. Exposure to modest heat (39 or 41 degrees C) resulted in rapid and sustained increases in HSP expression; and inhibition of HSP expression produced a marked increase in heat-induced increase in Caco-2 TJ permeability (P < 0.001). Heat exposure (41 degrees C) resulted in a compensatory increase in Caco-2 occludin protein expression and an increase in junctional localization. Inhibition of HSP expression prevented the compensatory upregulation of occludin protein expression and produced a marked disruption in junctional localization of occludin protein during heat stress. In conclusion, our findings demonstrate for the first time that a modest, physiologically relevant increase in temperature causes an increase in intestinal epithelial TJ permeability. Our data also show that HSPs play an important protective role in preventing the heat-induced disruption of intestinal TJ barrier and suggest that HSP mediated upregulation of occludin expression may be an important mechanism involved in the maintenance of intestinal epithelial TJ barrier function during heat stress.
机译：先前尚未研究过生理上相关的温度升高（37-41摄氏度）对肠上皮紧密连接（TJ）屏障的影响。此外，在热应激过程中，热休克蛋白（HSP）在调节肠TJ屏障中的作用仍然未知。由于热引起的肠TJ屏障紊乱可能在生理热应激期间导致内毒素血症和细菌移位，因此本研究的目的是研究温度适度，生理相关的温度升高（37-41摄氏度）对肠上皮TJ的影响屏障，并研究热休克蛋白对肠TJ屏障的保护作用。滤器生长的Caco-2肠上皮细胞被用作体外肠上皮模型系统，以评估热暴露对肠TJ屏障的影响。过滤器生长的Caco-2单层暴露于温度的适度升高（37-41摄氏度）导致Caco-2 TJ渗透率显着依赖时间和温度的升高。暴露于适度的热量（39或41摄氏度）会导致HSP表达持续快速增加。 HSP表达的抑制和热诱导Caco-2 TJ渗透性的增加显着增加（P <0.001）。高温（41​​摄氏度）导致Caco-2 occludin蛋白表达的补偿性增加和接合部位的增加。 HSP表达的抑制阻止了occludin蛋白表达的补偿性上调，并在热应激期间在occludin蛋白的连接定位中产生了明显的破坏。总而言之，我们的发现首次证明，温和的，与生理相关的温度升高会引起肠上皮TJ通透性的升高。我们的数据还表明，HSPs在防止热诱导的肠TJ屏障破坏中起重要的保护作用，并暗示HSP介导的occludin表达上调可能是在热应激期间维持肠上皮TJ屏障功能的重要机制。

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