Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Nutrients. 2020 Jan 28;12(2):343. doi: 10.3390/nu12020343.
Allergic airway diseases are accompanied by increased permeability and an inflammatory state of epithelial barriers, which are thought to be susceptible to allergen sensitization. Although exogenous drivers (proteases, allergens) of epithelial barrier disruption and sensitization are well studied, endogenous contributors (diet, xenobiotics, hormones, and metabolism) to allergic sensitization are much less understood. Xenoestrogens are synthetic or natural chemical compounds that have the ability to mimic estrogen and are ubiquitous in the food and water supply of developed countries. By interfering with the estrogen produced by the endocrine system, these compounds have the systemic potential to disrupt the homeostasis of multiple tissues. Our study examined the potential of prototypical xenoestrogen bisphenol A (BPA) to disrupt epithelial homeostasis and promote allergic responses . We found that BPA exposure in epithelial cultures significantly inhibited epithelial cell proliferation and wound healing, as well as promoted the expression of the innate alarmin cytokine TSLP in a time-and dose-dependent manner. , the exposure to BPA through water supply or inhalation induced a systemic para-inflammatory response by promoting the expression of innate inflammatory mediators in the skin, gut, and airway. In a murine tolerogenic antigen challenge model, chronic systemic exposure to BPA was sufficient to induce airway sensitization to innocuous chicken egg ovalbumin in the complete absence of adjuvants. Mechanistic studies are needed to test conclusively whether endocrine disruptors may play an upstream role in allergic sensitization via their ability to promote a para-inflammatory state.
变应性气道疾病伴有上皮屏障通透性增加和炎症状态，被认为易发生过敏原致敏。虽然上皮屏障破坏和致敏的外源性驱动因素（蛋白酶、过敏原）研究得很好，但对变应原致敏的内源性因素（饮食、外源性化学物质、激素和代谢）了解得较少。外源性雌激素是具有模拟雌激素能力的合成或天然化学化合物，在发达国家的食物和饮用水供应中普遍存在。这些化合物通过干扰内分泌系统产生的雌激素，具有全身性破坏多种组织内稳态的潜力。我们的研究检查了典型外源性雌激素双酚 A (BPA) 破坏上皮稳态和促进过敏反应的潜力。我们发现，上皮细胞培养物中 BPA 的暴露显著抑制了上皮细胞的增殖和伤口愈合，并以时间和剂量依赖的方式促进了先天警报素细胞因子 TSLP 的表达。通过水供应或吸入暴露于 BPA 会通过促进皮肤、肠道和气道中先天炎症介质的表达，引起全身性副炎症反应。在小鼠耐受原挑战模型中，慢性全身暴露于 BPA 足以在完全没有佐剂的情况下诱导对无害的鸡卵卵清蛋白的气道致敏。需要进行机制研究来明确测试内分泌干扰物是否可以通过促进副炎症状态，在上游发挥变应原致敏作用。
