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首页> 外文期刊>Life sciences >Influence of 8-bromo-cyclicAMP on interleukin-6 and-8 mRNA levels in A549 human lung epithelial cells exposed to organic dust: A time-kinetic study
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Influence of 8-bromo-cyclicAMP on interleukin-6 and-8 mRNA levels in A549 human lung epithelial cells exposed to organic dust: A time-kinetic study

机译：8-溴环AMP对有机尘暴露的A549人肺上皮细胞白细胞介素6和-8 mRNA水平的影响：时间动力学研究

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Exposure in a swine confinement building of previously unexposed subjects leads to an intense inflammatory reaction with increased number of inflammatory cells and mediators in the upper and lower respiratory tract. In vitro the organic dust induces cytokine release from respiratory epithelial cells. Whether the dust-induced release of IL-6 and IL-8 protein from A549 lung epithelial cells is a result of sustained mRNA expression during the 24 h exposure generally applied is unknown. Furthermore, it is not known if the previously demonstrated effects on basal and dust-induced IL-6 and IL-8 protein production by 8-bromo-cyclicAMP are time-dependent, since only cumulative effects are observed by measurement of cytokine release. In the present study reverse transcription(RT-) PCR was applied to investigate expression of IL-6 and IL-8 mRNA in A549 cells exposed to organic dust in a time-kinetic manner. The dust increased IL-6 and LL-8 mRNA expression at all times tested (1 h48 h). The IL-6 mRNA expression peaked at 1-1.5 h and was reduced with time, whereas the dust-induced IL-8 mRNA expression remained elevated. At 1-1.5 h, 8-bromo-cAMP stimulated basal and dust-induced IL-6 mRNA expression and attenuated dust-induced IL-8 mRNA expression by activation of protein kinase A- (PKA), as assessed with the PKA inhibitor H-89. On prolonged exposure (>3 h), the dust-induced IL-6 mRNA was PKA-dependently decreased, whereas at 17 h and longer the IL-8 mRNA expression induced by a dust-suspension with 8-bromo-cAMP was similar to, or enhanced, relative to the dust-induced IL-8 mRNA. Thus, 8-bromo-cAMP exerted opposite action on dust-induced IL-6 and IL-8 mRNA expression with time. (C) 2004 Elsevier Inc. All rights reserved.
机译：先前未暴露对象的猪禁闭室中的暴露导致强烈的炎症反应，上呼吸道和下呼吸道的炎症细胞和介体数量增加。在体外，有机尘土诱导呼吸道上皮细胞释放细胞因子。尚不清楚尘埃诱导的A549肺上皮细胞释放IL-6和IL-8蛋白是否是在通常应用的24 h暴露期间持续表达mRNA的结果。此外，由于通过测量细胞因子的释放仅观察到累积作用，因此先前证实的对8-溴环AMP对基础和粉尘诱导的IL-6和IL-8蛋白产生的影响是否是时间依赖性的，尚不清楚。在本研究中，采用逆转录（RT-）PCR技术以时间动态方式研究了暴露于有机尘埃的A549细胞中IL-6和IL-8 mRNA的表达。在所有测试时间（1小时48小时），灰尘均增加了IL-6和LL-8 mRNA的表达。 IL-6 mRNA表达在1-1.5 h达到峰值，并随时间降低，而粉尘诱导的IL-8 mRNA表达仍然升高。在1-1.5小时，通过激活蛋白激酶A-（PKA），8-溴cAMP刺激了基础和粉尘诱导的IL-6 mRNA表达，并减弱了粉尘诱导的IL-8 mRNA表达，用PKA抑制剂H评估-89。长时间暴露（> 3小时），粉尘诱导的IL-6 mRNA依赖于PKA降低，而在17小时或更长时间，由8-溴-cAMP悬浮液诱导的IL-8 mRNA表达与，或相对于粉尘诱导的IL-8 mRNA增强。因此，随着时间的推移，8-溴-cAMP对粉尘诱导的IL-6和IL-8 mRNA表达发挥相反的作用。 （C）2004 Elsevier Inc.保留所有权利。

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