Department of Pharmacology & Toxicology, College of Pharmacy, King Saud University, PO Box 2455, Riyadh 11451, Saudi Arabia.
Department of Pharmacology & Toxicology, College of Pharmacy, King Saud University, PO Box 2455, Riyadh 11451, Saudi Arabia.
Environ Res. 2018 Jul;164:327-339. doi: 10.1016/j.envres.2018.02.039. Epub 2018 Mar 20.
In recent decades, there has been a gradual increase in the prevalence of asthma. Various factors including environmental pollutants have contributed to this phenomenon. Plasticizer, di(2-ethylhexyl)phthalate (DEHP) is one of the commonest environmental pollutants due to its association with plastic products. DEHP gets released from plastic products easily leading to respiratory exposure in humans. As a consequence, DEHP is associated with allergic asthma in humans and animals. DEHP is reported to act as an adjuvant in ovalbumin-induced mouse models of asthma at high doses. However, these studies mostly looked into the role of DEHP on Th2 cytokines/eosinophilic inflammation without investigating the role of airway epithelial cells (AECs)/dendritic cells (DCs)/Th17 cells. Its adjuvant activity with natural allergens such as cockroach allergens at tolerable daily intake needs to be explored. Cockroach allergens and DEHP may be inhaled together due to their coexistence in work place as well as household environments. Therefore, effect of DEHP was assessed in cockroach allergens extract (CE)-induced mouse model of asthma. Airway inflammation, histopathology, mucus secretion, and immune responses related to Th2/Th17/DCs and AECs were assessed in mice with DEHP exposure alone and in combination with CE. Our study shows that DEHP converts CE-induced eosinophilic inflammation into mixed granulocytic inflammation by promoting Th2 as well as Th17 immune responses. This was probably due to downregulation of E-cadherin in AECs, and enhancement of costimulatory molecules (MHCII/CD86/CD40)/pro-inflammatory cytokines (IL-6/MCP-1) in DCs by DEHP. This suggests that DEHP facilitates development of mixed granulocytic airway inflammation in the presence of a natural allergen.
近几十年来,哮喘的患病率逐渐增加。各种因素,包括环境污染物,促成了这一现象。增塑剂邻苯二甲酸二(2-乙基己基)酯(DEHP)由于与塑料制品有关,是最常见的环境污染物之一。DEHP 很容易从塑料制品中释放出来,导致人类呼吸暴露。因此,DEHP 与人类和动物的过敏性哮喘有关。据报道,DEHP 在高剂量下作为卵清蛋白诱导的哮喘小鼠模型中的佐剂发挥作用。然而,这些研究大多关注 DEHP 对 Th2 细胞因子/嗜酸性粒细胞炎症的作用,而没有研究气道上皮细胞(AECs)/树突状细胞(DCs)/Th17 细胞的作用。需要探索其与天然过敏原(如蟑螂过敏原)在可耐受日摄入量下的佐剂活性。蟑螂过敏原和 DEHP 可能由于它们在工作场所和家庭环境中的共存而一起被吸入。因此,评估了 DEHP 在蟑螂过敏原提取物(CE)诱导的哮喘小鼠模型中的作用。在单独暴露于 DEHP 和与 CE 联合暴露于 DEHP 的小鼠中,评估了气道炎症、组织病理学、黏液分泌以及与 Th2/Th17/DCs 和 AECs 相关的免疫反应。我们的研究表明,DEHP 通过促进 Th2 和 Th17 免疫反应,将 CE 诱导的嗜酸性粒细胞炎症转化为混合粒细胞炎症。这可能是由于 DEHP 下调了 AECs 中的 E-钙粘蛋白,并增强了 DCs 中的共刺激分子(MHCII/CD86/CD40)/促炎细胞因子(IL-6/MCP-1)。这表明 DEHP 在存在天然过敏原的情况下促进了混合粒细胞性气道炎症的发展。
Toxicol Appl Pharmacol. 2013-12-24
J Diabetes Metab Disord. 2025-1-25
World Allergy Organ J. 2023-11-19
Front Pharmacol. 2023-1-9
Environ Sci Pollut Res Int. 2019-7-31