ABSTRACT

Acute-phase response (APR) is an innate stress reaction to tissue trauma or injury, infection, and environmental insults like ozone (O₃). Regardless of the location of stress, the liver has been considered the primary contributor to circulating acute-phase proteins (APPs); however, the mechanisms underlying APR induction are unknown. Male Wistar–Kyoto rats were exposed to air or O₃ (1 ppm, 6-hr/day, 1 or 2 days) and examined immediately after each exposure and after 18-hr recovery for APR proteins and gene expression. To assess the contribution of adrenal-derived stress hormones, lung and liver global gene expression data from sham and adrenalectomized rats exposed to air or O₃ were compared for APR transcriptional changes. Data demonstrated serum protein alterations for selected circulating positive and negative APPs following 2 days of O₃ exposure and during recovery. At baseline, APP gene expression was several folds higher in the liver relative to the lung. O₃-induced increases were significant for lung but not liver for some genes including orosomucoid-1. Further, comparative assessment of mRNA seq data for known APPs in sham rats exhibited marked elevation in the lung but not liver, and a near-complete abolishment of APP mRNA levels in lung tissue of adrenalectomized rats. Thus, the lung appears to play a critical role in O₃-induced APP synthesis and requires the presence of circulating adrenal-derived stress hormones. The relative contribution of lung versus liver and the role of neuroendocrine stress hormones need to be considered in future APR studies involving inhaled pollutants.

摘要

急性期反应 (APR) 是对组织创伤或损伤、感染和臭氧 (O ₃ ) 等环境损害的先天应激反应。无论压力的位置如何，肝脏都被认为是循环急性期蛋白 (APP) 的主要贡献者。然而，APR 诱导的机制尚不清楚。雄性 Wistar–Kyoto 大鼠暴露于空气或 O ₃（1 ppm，6 小时/天，1 或 2 天），并在每次暴露后和 18 小时恢复后立即检查 APR 蛋白和基因表达。评估来自暴露于空气或 O _{3的假大鼠和肾上腺切除大鼠的肾上腺源性应激激素、肺和肝全局基因表达数据的贡献}比较了 APR 转录变化。_{数据表明，在 O 3}暴露 2 天后和恢复期间，选定的循环阳性和阴性 APP 的血清蛋白改变。在基线时，肝脏中的 APP 基因表达相对于肺部高几倍。对于包括 orosomucoid-1 在内的一些基因， O ₃诱导的增加对肺有显着影响，但对肝脏没有影响。此外，对假手术大鼠已知 APP 的 mRNA seq 数据的比较评估显示，在肺而非肝脏中显着升高，并且肾上腺切除大鼠肺组织中 APP mRNA 水平几乎完全消失。因此，肺似乎在 O _{3中起关键作用}- 诱导的 APP 合成，需要存在循环的肾上腺源性应激激素。在未来涉及吸入污染物的 APR 研究中，需要考虑肺与肝脏的相对贡献以及神经内分泌应激激素的作用。