Abstract

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 3ˈ untranslated region (3ˈ 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.