Toll-like receptor 4 is a key regulator of asthma exacerbation caused by aluminum oxide nanoparticles via regulation of NF-?B phosphorylation

Aluminum oxide nanoparticles (Al2O3 NPs) have recently been reported to cause an inflammatory response in the lungs, and studies are being conducted on their adverse effects, especially in patients with underlying lung diseases such as asthma. However, the underlying mechanism of asthma aggravation caused by Al2O3 NPs re-mains unclear. This study investigated whether Al2O3 NPs exacerbate ovalbumin (OVA)-induced asthma and focused on the correlation between toll-like receptor 4 (TLR4) signaling and Al2O3 NP-induced asthma exacer-bation. Al2O3 NP exposure in asthmatic mice resulted in increased inflammatory cell counts in the lungs, airway hyperresponsiveness, and increased levels of inflammatory cytokines compared with only OVA-induced mice, and excessive secretion of mucus was observed in the airways. Moreover, Al2O3 NP exposure in OVA-induced mice increased the expression levels of TLR4, phospho-nuclear transcription factor-kappa B (p-NF kappa B), myeloid differentiation factor 88 (MyD88), and phospho-NF kappa B inhibitor alpha (p-IxB alpha). Furthermore, in the lungs of TLR4 knockout mice exposed to Al2O3 NPs and in a human airway epithelial cell line with down regulated TLR4, the expression levels of MyD88, p-NFxB, and p-IxB alpha were decreased, and asthma-related allergic responses were reduced. Therefore, we demonstrated that TLR4 is important for aggravation of asthma induced by Al2O3 NPs, and this study provides useful information regarding as yet undiscovered novel target signaling.

Automated summary

This study investigates the exacerbation of asthma induced by aluminum oxide nanoparticles (Al2O3 NPs) and explores the correlation between toll-like receptor 4 (TLR4) signaling and Al2O3 NP-induced asthma exacerbation. The results show that Al2O3 NP exposure leads to increased inflammatory cell counts, airway hyperresponsiveness, and inflammatory cytokine levels in asthmatic mice. The expression levels of TLR4 and related signaling proteins are also affected by Al2O3 NP exposure.