MiR-193b-3p Regulates TLR4 Expression to Inhibit Inflammation by Targeting ETS1 in Allergic Rhinitis

Abstract

<b><i>Introduction:</i></b> Allergic rhinitis (AR) is identified as a multifactorial disease caused by the interaction of genes and surroundings, which is difficult to cure. MicroRNAs were reported to be engaged in AR development. Here, we aimed to seek the anti-inflammatory effects and regulatory mechanism of <i>miR-193b-3p</i> in AR. <b><i>Methods:</i></b> Mucosal tissues from AR patients and healthy volunteers were collected, and human nasal epithelial cells (HNECs) were treated with IL-13 to establish a cell model of AR. The gene expression of <i>miR-193b-3p</i>, ETS1, TLR4, GM-CSF, <i>eotaxin</i>, and MUC5AC was determined by RT-qPCR. The protein levels of ETS1 and TLR4 were examined using Western blot. Enzyme-linked immunosorbent assay was performed to measure protein concentration of GM-CSF, eotaxin, and MUC5AC in cell supernatant. Dual luciferase assay was applied to verify the interaction among <i>miR-193b-3p</i>, ETS1, and <i>TLR4</i>. <b><i>Results:</i></b> The expression of m<i>iR-193b-3p</i> was declined in clinical samples from AR patients and in IL-13-induced HNECs, while the mRNA and protein levels of ETS1 and TLR4 were elevated. <i>MiR-193b-3p</i> overexpression or ETS1 silencing notably decreased the mRNA and protein levels of GM-CSF, eotaxin, and MUC5AC in IL-13-treated HNECs. Mechanistically, <i>miR-193b-3p</i> directly combined with <i>ETS1</i> to silence <i>ETS1</i> expression. ETS1 promoted the transcriptional activity of <i>TLR4</i> through interacting with <i>TLR4</i> promoter. Furthermore, rescue experiments revealed that ETS1 overexpression abolished <i>miR-193b-3p</i> sufficiency-mediated suppression of the mRNA and protein levels of GM-CSF, eotaxin, and MUC5AC in IL-13-treated HNECs. Similarly, TLR4 overexpression compromised the inhibitory impacts of ETS1 downregulation on the mRNA and protein levels of GM-CSF, eotaxin, and MUC5AC in IL-13-induced HNECs. <b><i>Discussion:</i></b> <i>MiR-193b-3p</i> repressed IL-13-induced inflammatory response in HNECs by suppressing <i>ETS1</i>/<i>TLR4</i> axis, which indicated that <i>miR-193b-3p</i> might be a therapeutic target for AR treatment.