Wirth Delphine, Christians Elisabeth, Munaut Carine, Dessy Cécile, Foidart Jean-Michel, Gustin Pascal
Department of Histology and Embryology, Faculty of Veterinary Medicine, University of Liege, 4000 Liege, Belgium.
Cell Stress Chaperones. 2002 Oct;7(4):387-95. doi: 10.1379/1466-1268(2002)007<0387:dhsghr>2.0.co;2.
Members of heat shock proteins (Hsp70) family have been considered to respond to a large variety of stressful conditions. But it was suggested that, in pulmonary cells, Hsp response depends more closely on the type of stimulus. The lungs are critical organs potentially subjected to air pollution affecting respiratory function and, therefore, these organs are of particular interest with regard to the stress response. To investigate the stress dependence of Hsp70 response in lungs, we created transgenic mice where the firefly luciferase reporter gene is under the control of the murine hsp70-1 promoter and exposed them to different sublethal toxic conditions. For each condition, the level of transgene induction and pulmonary toxicity were assessed. We found that hsp70-1 promoter was stimulated by heat shock and cadmium but not by ozone, paraquat, and parathion, even if these chemicals induced respiratory distress and lung inflammation. Similar observations were made when expression of the endogenous hsp70-1 gene was analyzed, indicating that our transgenic model was accurately detecting hsp70-1 induction. Thereby, it appeared that hsp70-1 response is selective and depends on signaling pathways triggered by the toxicants rather than by their pathologic toxicity per se. Furthermore, because all the chemicals used in our study have been previously described to increase the level of oxidative stress, it indicates that there is no direct and simple correlation between hsp70-1 response and the level of oxidative stress, but more specific oxidative patterns should be involved in Hsp regulation.
热休克蛋白（Hsp70）家族成员被认为可对多种应激条件作出反应。但有人提出，在肺细胞中，Hsp反应更紧密地依赖于刺激的类型。肺是可能受到影响呼吸功能的空气污染的关键器官，因此，这些器官在应激反应方面特别受关注。为了研究肺中Hsp70反应的应激依赖性，我们构建了转基因小鼠，其中萤火虫荧光素酶报告基因受小鼠hsp70 - 1启动子的控制，并将它们暴露于不同的亚致死毒性条件下。对于每种条件，评估转基因诱导水平和肺毒性。我们发现hsp70 - 1启动子受到热休克和镉的刺激，但不受臭氧、百草枯和对硫磷的刺激，即使这些化学物质诱导了呼吸窘迫和肺部炎症。在分析内源性hsp70 - 1基因的表达时也有类似的观察结果，表明我们的转基因模型准确地检测到了hsp70 - 1的诱导。由此看来，hsp70 - 1反应具有选择性，并且依赖于由毒物触发的信号通路，而不是其本身的病理毒性。此外，因为我们研究中使用的所有化学物质先前都被描述为会增加氧化应激水平，这表明hsp70 - 1反应与氧化应激水平之间没有直接和简单的相关性，但更特定的氧化模式应该参与Hsp调节。
