Xu Yanqiu, Feng Yanming, Wang Ling, Xu Xin, Xu Li, Wang Bohan
Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, P.R. China.
Nanjing Jiangning Hospital of Chinese Medicine/Jiangning Chinese Medicine Hospital Affiliated to China Pharmaceutical University, Nanjing, Jiangsu 211100, P.R. China.
Int J Mol Med. 2025 Sep;56(3). doi: 10.3892/ijmm.2025.5573. Epub 2025 Jul 4.
Air pollutants contribute to the occurrence and development of asthma by impairing the airway epithelial barrier. However, underlying molecular mechanisms remain unknown. The present study investigated whether co‑exposure to the air pollutant benzo[a]pyrene (BaP) and ovalbumin (OVA) enhanced OVA‑induced epithelial tight junction disruption and explored the potential mechanisms involved. Asthma mouse and airway epithelial cell models were established and exposed to BaP. Lung pathology, immunoglobulin E (IgE), tight junction proteins zonula occludens‑1 (ZO‑1) and occludin, reactive oxygen species (ROS), NOD‑like receptor protein 3 (NLRP3), apoptosis‑associated speck‑like protein containing a CARD, caspase‑1, interleukin (IL)‑18 and IL‑1β were assessed by hematoxylin‑eosin staining, enzyme‑linked immunosorbent assay, western blotting, immunohistochemistry and immunofluorescence. Inhibitors of ROS and NLRP3 were used to assess their effect on ZO‑1 and occludin and downstream signaling pathways to clarify BaP‑induced damage. Lung tissue damage was exacerbated by BaP, the IgE level increased and the ZO‑1 and occludin expression reduced in both models, thereby disrupting airway epithelial tight junctions. Additionally, BaP increased ROS levels and activated the NLRP3/caspase‑1 signaling pathway. However, reducing ROS and NLRP3 restored the ZO‑1 and occludin expression and improved epithelial integrity. Airway tight junction disruption was promoted by BaP by activating the ROS‑driven NLRP3/caspase‑1 signaling pathway.
空气污染物通过损害气道上皮屏障促进哮喘的发生和发展。然而，其潜在的分子机制仍不清楚。本研究调查了空气污染物苯并[a]芘（BaP）与卵清蛋白（OVA）共同暴露是否会增强OVA诱导的上皮紧密连接破坏，并探讨其中涉及的潜在机制。建立哮喘小鼠和气道上皮细胞模型并使其暴露于BaP。通过苏木精-伊红染色、酶联免疫吸附测定、蛋白质印迹法、免疫组织化学和免疫荧光法评估肺病理学、免疫球蛋白E（IgE）、紧密连接蛋白闭合蛋白1（ZO-1）和闭合蛋白、活性氧（ROS）、NOD样受体蛋白3（NLRP3）、含半胱天冬酶激活和招募结构域的凋亡相关斑点样蛋白、半胱天冬酶-1、白细胞介素（IL）-18和IL-1β。使用ROS和NLRP3抑制剂评估它们对ZO-1和闭合蛋白以及下游信号通路的影响，以阐明BaP诱导的损伤。BaP加剧了肺组织损伤，两个模型中的IgE水平均升高，ZO-1和闭合蛋白表达降低，从而破坏了气道上皮紧密连接。此外，BaP增加了ROS水平并激活了NLRP3/半胱天冬酶-1信号通路。然而，降低ROS和NLRP3可恢复ZO-1和闭合蛋白的表达并改善上皮完整性。BaP通过激活ROS驱动的NLRP3/半胱天冬酶-1信号通路促进气道紧密连接破坏。
