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首页> 外文期刊>Environmental research >Stress axis variability is associated with differential ozone-induced lung inflammatory signaling and injury biomarker response
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Stress axis variability is associated with differential ozone-induced lung inflammatory signaling and injury biomarker response

机译：应力轴变异性与臭氧诱导的肺炎性信号转导和损伤生物标志物反应相关

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Ozone (O-3), a ubiquitous urban air pollutant, causes adverse pulmonary and extrapulmonary effects. A large variability in acute O-3-induced effects has been observed; however, the basis for interindividual differences in susceptibility is unclear. We previously demonstrated a role for the hypothalamic-pituitary-adrenal (HPA) stress axis and glucocorticoid response in acute O-3 toxicity. Glucocorticoids have important anti-inflammatory actions, and have been shown to regulate lung inflammatory responses. We hypothesised that a hyporesponsive HPA axis would be associated with greater O-3-dependent lung inflammatory signaling. Two genetically-related rat strains with known differences in stress axis reactivity, highly-stress responsive Fischer (F344) and less responsive Lewis (LEW), were exposed for 4 h by nose-only inhalation to clean air or 0.8 ppm O-3, and euthanized immediately after exposure. As expected, baseline (air-exposed) plasma corticosterone was significantly lower in the hypo stress responsive LEW. Although O-3 exposure increased plasma corticosterone in both strains, corticosterone remained significantly lower in LEW when compared to F334. LEW exhibited greater O-3-induced inflammatory cytokine/chemokine signaling compared to F344, consistent with the lower corticosterone levels. Since we observed strain-specific differences in inflammatory signaling, we further investigated injury biomarkers (total protein, albumin and lactate dehydrogenase). Although the hyper-responsive F344 exhibited lower inflammatory signaling in response to O-3 compared with LEW, they had greater levels of lung injury biomarkers. Our results indicate that stress axis variability is associated with differential O-3-induced lung toxicity. Given the large variability in stress axis reactivity among humans, stress axis regulation could potentially be a determining factor underlying O-3 sensitivity.
机译：臭氧（O-3）是一种普遍存在的城市空气污染物，会对肺和肺外产生不利影响。观察到急性O-3诱导的作用有很大的差异。然而，个体间药敏性差异的基础尚不清楚。我们先前证明了下丘脑-垂体-肾上腺（HPA）应力轴和糖皮质激素反应在急性O-3毒性中的作用。糖皮质激素具有重要的抗炎作用，并已显示出可调节肺部炎症反应。我们假设低反应性HPA轴将与更大的O-3依赖性肺炎性信号传导相关。通过仅鼻子吸入的方式将两种具有已知应力轴反应性差异的遗传相关大鼠品系，即高应力反应性Fischer（F344）和反应性较低的Lewis（LEW），暴露于空气中或暴露于0.8 ppm O-3的纯空气中暴露4小时，并在接触后立即安乐死。正如预期的那样，低应激反应性左心室的基线（空气暴露）血浆皮质酮显着降低。尽管O-3暴露增加了这两种菌株的血浆皮质酮，但与F334相比，LEW中的皮质酮仍然显着降低。与F344相比，LEW表现出更大的O-3诱导的炎性细胞因子/趋化因子信号传导，与较低的皮质酮水平一致。由于我们在炎症信号中观察到了菌株特异性差异，因此我们进一步研究了损伤生物标志物（总蛋白，白蛋白和乳酸脱氢酶）。尽管与LEW相比，高反应性F344对O-3的反应显示出较低的炎症信号传导，但它们具有较高水平的肺损伤生物标志物。我们的结果表明，应力轴变异性与O-3诱导的不同肺毒性有关。考虑到人类在应激轴反应性方面的巨大差异，应激轴调节可能是O-3敏感性的决定因素。

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