Citation:

Alewel, D., A. Henriquez, C. Colonna, S. Snow, Mette C. Schladweiler, C. Miller, AND U. Kodavanti. Ozone-Induced Acute Phase Response in Lung Versus Liver: The Role of Adrenal-Derived Stress Hormones. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH - PART A: CURRENT ISSUES. Taylor & Francis, Inc., Philadelphia, PA, 84(6):235-248, (2021). https://doi.org/10.1080/15287394.2020.1858466

Impact/Purpose:

Air pollutants are known to induce a stress response after inhalation. This stress response is associated with an acute phase response induction from host to protect one from stressor-induced injury. It is believed that the proteins involved in this stress response which are released into the circulation come from liver. Our data show that lung may also contribute to these proteins since gene expression for acute phase proteins is markedly increased in the lung but not liver. We further show that adrenal-derived stress hormones are necessary for the development of acute phase response and that this response is mediated through the central stress axis activation. Thus, these data provide insights on how stress response is generated and what is the relative contribution of liver versus lung.

Description:

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.

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