Hodge Myles X, Henriquez Andres R, Kodavanti Urmila P
Oak Ridge Institute for Science and Education Research Participation Program, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Public Health and Integrated Toxicology Division, Center for Public Health and Environmental Assessment, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Toxics. 2021 Jun 4;9(6):132. doi: 10.3390/toxics9060132.
Adrenergic receptors (ARs) and glucocorticoid receptors (GRs) are activated by circulating catecholamines and glucocorticoids, respectively. These receptors regulate the homeostasis of physiological processes with specificity via multiple receptor subtypes, wide tissue-specific distribution, and interactions with other receptors and signaling processes. Based on their physiological roles, ARs and GRs are widely manipulated therapeutically for chronic diseases. Although these receptors play key roles in inflammatory and cellular homeostatic processes, little research has addressed their involvement in the health effects of air pollution. We have recently demonstrated that ozone, a prototypic air pollutant, mediates pulmonary and systemic effects through the activation of these receptors. A single exposure to ozone induces the sympathetic-adrenal-medullary and hypothalamic-pituitary-adrenal axes, resulting in the release of epinephrine and corticosterone into the circulation. These hormones act as ligands for ARs and GRs. The roles of beta AR (βARs) and GRs in ozone-induced pulmonary injury and inflammation were confirmed in a number of studies using interventional approaches. Accordingly, the activation status of ARs and GRs is critical in mediating the health effects of inhaled irritants. In this paper, we review the cellular distribution and functions of ARs and GRs, their lung-specific localization, and their involvement in ozone-induced health effects, in order to capture attention for future research.
肾上腺素能受体(ARs)和糖皮质激素受体(GRs)分别被循环中的儿茶酚胺和糖皮质激素激活。这些受体通过多种受体亚型、广泛的组织特异性分布以及与其他受体和信号传导过程的相互作用,特异性地调节生理过程的稳态。基于其生理作用,ARs和GRs在慢性疾病的治疗中被广泛应用。尽管这些受体在炎症和细胞稳态过程中起关键作用,但很少有研究探讨它们在空气污染对健康影响中的作用。我们最近证明,作为典型空气污染物的臭氧,通过激活这些受体介导肺部和全身效应。单次暴露于臭氧会诱导交感 - 肾上腺髓质轴和下丘脑 - 垂体 - 肾上腺轴,导致肾上腺素和皮质酮释放到循环中。这些激素作为ARs和GRs的配体。多项干预性研究证实了β肾上腺素能受体(βARs)和GRs在臭氧诱导的肺损伤和炎症中的作用。因此,ARs和GRs的激活状态在介导吸入性刺激物对健康的影响中至关重要。在本文中,我们综述了ARs和GRs的细胞分布与功能、它们在肺部的特异性定位以及它们在臭氧诱导的健康影响中的作用,以期引起未来研究的关注。