Huffman L J, Prugh D J, Brumbaugh K, Ding M
Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505, USA.
Inhal Toxicol. 2002 Nov;14(11):1161-74. doi: 10.1080/08958370290084845.
Results from previous studies indicate that hyperthyroidism increases the risk of ozone-induced lung toxicity. To better understand the processes that might contribute to the increased pulmonary inflammatory response to ozone in hyperthyroidism, we evaluated bronchoalveolar lavage fluid levels of selected cytokines in control and hyperthyroid rats after exposure to air or ozone. In addition, we assessed whether there is a relative increase in nuclear factor-kappa B (NF-kappaB) binding activity in cells harvested by bronchoalveolar lavage from hyperthyroid rats following the inhalation of ozone. A hyperthyroid condition was induced by the administration of thyroxine (0.5 mg/kg body weight) for 7 days. Control rats received vehicle injections. The animals were then exposed by inhalation to air or ozone (2 ppm for 3 h) and studied 18 h following the exposure. Bronchoalveolar lavage levels of MIP-2 and MCP-1 were increased in both control and hyperthyroid rats by ozone exposure. However, the increases in hyperthyroid rats were much greater, MIP-2 1.5-fold and MCP-1 11-fold, when compared to levels in controls following ozone. These changes appeared to be relatively specific; bronchoalveolar lavage fluid levels of interleukin (IL)-6, IL-4, and IL-10 were generally low or nondetectable across all of the studied groups at the 18-h postexposure time point. We also found that NF-kappaB binding activity was increased at both 4 and 18 h following ozone exposure in bronchoalveolar lavage cell extracts from hyperthyroid rats relative to the activity in control samples. Collectively, these results suggest that mechanisms contributing to the enhanced pulmonary inflammatory response to ozone in a hyperthyroid state include an increase in NF-kappaB activation and an upregulation of chemokine production.
先前的研究结果表明，甲状腺功能亢进会增加臭氧诱导的肺毒性风险。为了更好地理解可能导致甲状腺功能亢进时肺部对臭氧炎症反应增加的过程，我们评估了暴露于空气或臭氧后的对照大鼠和甲状腺功能亢进大鼠支气管肺泡灌洗液中选定细胞因子的水平。此外，我们评估了甲状腺功能亢进大鼠吸入臭氧后，支气管肺泡灌洗收集的细胞中核因子-κB（NF-κB）结合活性是否相对增加。通过给予甲状腺素（0.5mg/kg体重）7天来诱导甲状腺功能亢进状态。对照大鼠接受赋形剂注射。然后动物通过吸入暴露于空气或臭氧（2ppm，3小时），并在暴露后18小时进行研究。臭氧暴露使对照大鼠和甲状腺功能亢进大鼠的支气管肺泡灌洗液中MIP-2和MCP-1水平均升高。然而，与臭氧暴露后的对照水平相比，甲状腺功能亢进大鼠的升高幅度要大得多，MIP-2升高了1.5倍，MCP-1升高了11倍。这些变化似乎相对具有特异性；在暴露后18小时的所有研究组中，白细胞介素（IL）-6、IL-4和IL-10的支气管肺泡灌洗液水平通常较低或无法检测到。我们还发现，与对照样品相比，甲状腺功能亢进大鼠支气管肺泡灌洗细胞提取物中臭氧暴露后4小时和18小时的NF-κB结合活性均增加。总体而言，这些结果表明，导致甲状腺功能亢进状态下肺部对臭氧炎症反应增强的机制包括NF-κB激活增加和趋化因子产生上调。
