Acute iron oxide nanoparticles exposure induced murine eosinophilic airway inflammation via TLR2 and TLR4 signaling.

Liang Yue, Li Qidian, Wang Jiawei, Xue Rou, He Miao

Environmental toxicology 2022 Apr

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Iron oxide nanoparticles (Fe2 O3 NPs) is the main component of air pollution particles in urban rail transit environment. People are more exposed to Fe2 O3 NPs, however, the studies on relationship between Fe2 O3 NPs and respiratory health are limited. In the present study, acute airway inflammation caused by Fe2 O3 NPs and its possible mechanism were investigated. BALB/c mice were intratracheally challenged with different concentrations of Fe2 O3 NPs. Fe2 O3 NPs induced bronchial epithelial barrier function damage, infiltration of neutrophils and lymphocytes into the airway submucosa, secretion of mucus in the airway epithelium and elevated expression of eosinophil major basic protein (EMBP) in lungs. Compared with the control group, Fe2 O3 NPs increased eosinophils by 20 times in bronchoalveolar lavage fluid (BALF), and markedly increased eosinophils related cytokines and chemokines, including interleukin (IL) -5, IL-33, thymic stromal lymphopoietin (TSLP), monocyte chemotactic protein (MCP)-3, eotaxin, tumor necrosis factor (TNF)-α, keratinocyte chemoattractant (KC). Furthermore, Fe2 O3 NPs up-regulated levels of IL-5, MCP-3, eotaxin, and KC in serum. In vitro studies showed that Fe2 O3 NPs increased the genes and proteins expression of Toll-like receptors (TLR)-2, TLR4, TNF receptor associated factor 6 (TRAF6), myeloid differentiation factor 88 (MyD88), nuclear factor (NF)-κB, and TNF-α in RAW267.4 cells. The downstream inflammatory cytokine protein expression and release such as TNF-α was significantly decreased after using TLR2/TLR4 inhibitor OxPAPC, but not MyD88 inhibitor ST2825. These results suggest that TLR2 and TLR4 played important role in Fe2 O3 NPs inducing acute eosinophilic airway inflammation in the murine lung. © 2022 Wiley Periodicals LLC.

Citation

Liang Yue, Li Qidian, Wang Jiawei, Xue Rou, He Miao. Acute iron oxide nanoparticles exposure induced murine eosinophilic airway inflammation via TLR2 and TLR4 signaling. Environmental toxicology. 2022 Apr;37(4):925-935