MiR-140-5p/TLR4 /NF-κB signaling pathway: Crucial role in inflammatory response in 16HBE cells induced by dust fall PM2.5

Fine atmospheric particles with a diameter of 2.5 µm or less (PM_2.5) have a large specific surface area, and carry a variety of organic matter, heavy metals, Minerals and bacteria. They are an important risk factor in human non-communicable disease. To explore the molecular regulatory mechanism of the airway inflammation caused by PM_2.5, an in vitro human bronchial epithelial (16HBE) cells poisoning model was deployed. Results showed that PM_2.5 had a strong inhibitory effect on cells viability, and induced cells to secrete high levels of IL-6 and CXCL 8. These two biomarkers of inflammation were significantly reduced in the presence of TAK 242. TLR4, MyD88, IKK, and p-p65 proteins were highly expressed on exposure to PM_2.5. Pretreatment with TAK 242 interfered with the activation of the TLR4 signaling pathway. By detecting the presence of lipopolysaccharides (LPS) in PM_2.5 which had been autoclaved, it was speculated that the activation of the TLR4/NF-κB signaling pathway may be mediated by LPS. It was demonstrated using gain- and loss- function experiments that miR-140-5p negatively regulated TLR4 to mediate inflammation in 16HBE cells. The dual-luciferase reporter assay confirmed that miR-140-5p directly binds to the 3' untranslated region (3' UTR) of TLR4 to initiate biological activity. In conclusion, this study revealed a new mechanism by which the miR-140-5p/TLR4 signaling pathway mediated the inflammatory response of 16HBE cells induced by PM_2.5. Differential expression of miRNA, and the activation of the TLR4/NF-κB signaling pathway induced by PM_2.5 implicates PM_2.5 in the pathogenesis of airway inflammation.