Effect of Heat Stress on Lipopolysaccharide-Induced Vascular Permeability Change in Mice
Effect of Heat Stress on Lipopolysaccharide-Induced Vascular Permeability Change in Mice
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DOI：
10.1124/jpet.102.035758
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发表时间：
2002-11
影响因子：
3.5
通讯作者：
Taiyo Suganuma;K. Irie;E. Fujii;T. Yoshioka;T. Muraki
中科院分区：
文献类型：
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作者：
Taiyo Suganuma;K. Irie;E. Fujii;T. Yoshioka;T. Muraki
以小鼠作为炎症介质诱导的炎症反应模型，研究了热休克蛋白（hsp）诱导对脂多糖（LPS）诱导的血管通透性增加的影响。将小鼠暴露在43°C的环境温度下1小时，然后恢复到23°C以恢复长达24小时。热暴露后6 h，热休克蛋白70（hsp 70）和热休克蛋白90（hsp 90）含量升高，24 h恢复到基础水平，热休克相关蛋白70（hsc 70）含量无明显变化。在热暴露后0、2、4、6或24 h皮下注射LPS。LPS注射后2小时，通过静脉注射的染料的皮肤累积来评估血管渗透性。LPS诱导的染料泄漏减少了42和49%，在热暴露小鼠恢复后4和6小时，分别。热应激恢复6 h后，LPS诱导的小鼠皮肤肿瘤坏死因子-α（TNF-α）和前列腺素E2（PGE 2）含量的升高明显降低。LPS诱导的环氧合酶-2 mRNA的增加在热应激小鼠中减弱，但TNF-α mRNA的增加没有减弱。热休克蛋白70和热休克蛋白90的抑制剂脱氧精胍菌素和热休克蛋白90的特异性抑制剂格尔德霉素可剂量依赖性地逆转热应激对LPS诱导的染料渗漏和真皮TNF-α含量的抑制作用，但对PGE 2含量无影响。这些结果表明，热应激通过诱导热休克蛋白90，导致抑制TNF-α的产生减弱LPS诱导的血管通透性变化。
The effect of heat shock protein (hsp) induction on lipopolysaccharide (LPS)-induced increase in vascular permeability was studied in mice as a model of inflammatory mediator-induced inflammatory response. Mice were exposed to an ambient temperature of 43°C for 1 h and then returned to 23°C to recover up to 24 h. Dermal contents of hsp70 and hsp90 but not heat shock cognate protein (hsc)70 increased at 6 h after heat exposure and returned to the basal level at 24 h. LPS was injected subcutaneously at 0, 2, 4, 6, or 24 h after heat exposure. Two hours after LPS injection, vascular permeability was assessed by dermal accumulation of intravenously injected dye. LPS-induced dye leakage was reduced by 42 and 49% in heat-exposed mice after recovery for 4 and 6 h, respectively. Increases in dermal tumor necrosis factor-α (TNF-α) and prostaglandin E2 (PGE2) contents induced by LPS were significantly reduced in the heat-stressed mice recovered for 6 h. LPS-induced increase in cyclooxygenase-2 but not TNF-α mRNA was attenuated in heat-stressed mice. Deoxyspergualin, an inhibitor of hsc70 and hsp90, and geldanamycin, a specific hsp90 inhibitor, dose dependently reversed the inhibitory effect of heat stress on LPS-induced dye leakage and dermal TNF-α content but not PGE2 content. These results suggest that heat stress attenuated LPS-induced vascular permeability change by inducing hsp90, leading to inhibition of TNF-α production.