Mono-n-butyl phthalate regulates nuclear factor erythroid 2-related factor 2 and nuclear factor kappa B pathway in an ovalbumin-induced asthma mouse model

Recent studies have emphasized the role of endocrine-disrupting chemicals in asthma development, especially in eosinophilic asthma. However, the exact mechanism was unknown. Among all the endocrine-disrupting chemicals, mono-n-butyl phthalate (MnBP) was a chemical that was most frequently detected in human urine. Our study was performed with the aim of investigating the harmful effects of MnBP on airway epithelial cells (AECs), T cells, and eosinophils by using eosinophilic asthma mouse models. Mice that received OVA with MnBP had higher levels of airway hyperresponsiveness, total and eosinophil cell counts, as well as T cell proliferation and T helper 2 cytokine release than those which only received OVA. Moreover, MnBP contributed to directly enhancing the eosinophilic activation which was shown in. Long-term exposure MnBP activated AECs through the nuclear factor kappa B (NF-kB) pathway, decreased nuclear factor erythroid 2-related factor 2 (Nrf2) expression, and increased interleukin-33 expression. Additionally, MnBP can induce human eosinophil activation to release eosinophil extracellular traps (EETs). Taken together, our study suggested the roles of MnBP exposure increase the risk of asthma development and severity. Furthermore, vitamin E treatment (anti-inflammatory and antioxidant effects) can reduce MnBP-induced harmful effects through inhibiting EETs, restoring Nrf2, and suppressing the NF-kB pathway.

Automated summary

Recent studies have found that endocrine-disrupting chemicals play a significant role in the development of asthma, particularly eosinophilic asthma. However, the specific mechanism remains unclear. This study used mouse models to investigate the harmful effects of mono-n-butyl phthalate (MnBP) on airway epithelial cells, T cells, and eosinophils. The results showed that MnBP increased airway hyperresponsiveness, eosinophil and T cell counts, and T helper 2 cytokine release in mice with asthma. Furthermore, MnBP directly enhanced eosinophil activation.