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Objective: Olfactory dysfunction (OD) is a common symptom of allergic rhinitis (AR) that can seriously affect patient quality of life; however, the associated pathogenesis remains unclear. This study aimed to explore the relationship between OD and damage of the olfactory bulb (OB) in allergic rhinitis (AR). The therapeutic potential of TAK-242, a selective TLR4 inhibitor, was evaluated for OD., Method: An AR mouse model was established with ovalbumin (OVA) to test the olfactory function of AR mice using the buried food pellet test (BFPT). Mice with OD were intraperitoneally injected with TAK-242 or 1% DMSO (vehicle). Immunohistochemistry was used to detect microglia and astrocyte activation in the OB. TUNNEL staining was performed to detect apoptosis in the OB. Proteins in the TLR4 signaling pathway were detected by Western blot. The level of proinflammatory factor mRNA in the OB was determined by RT-PCR., Result: Neuroinflammation was observed in the OB of the OD group, as evidenced by glial cell activation and increased proinflammatory factor expression. The number of apoptotic cells was significantly increased in the OB of the OD group. The expression of TLR4, MyD88, and p-NF-κBp65 was significantly up-regulated in the OB of the OD group. TAK-242 treatment significantly reduced the level of IL-1β, IL-6, and TNF-α mRNA expression, as well as activation of microglia and astrocytes in the OB tissues., Conclusion: TAK-242 improve olfactory function in AR mice mainly by reducing neuroinflammation and apoptosis in the OB, which may be related to blocking the TLR4/MyD88/NF-κB signaling pathway., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The present study aimed to investigate whether microRNA (miR)-31 exerted therapeutic potential in allergic rhinitis (AR) and to explore its underlying mechanism. Firstly, the expression levels of miR-31 were detected by reverse transcription-quantitative PCR in the nasal mucosa of patients and mice. Subsequently, an ovalbumin (OVA)-induced animal model of AR was constructed. Allergic symptom score, histopathological characteristics, OVA-specific immunoglobulin E (IgE) titers, and T-helper (Th)1 and Th2 cell-related cytokine levels were analyzed in OVA-sensitized mice, miR-31-overexpressing mice, miR-negative control mice and control mice. Furthermore, interleukin (IL)-13-stimulated nasal epithelial cells (NECs) were used to assess the effects of miR-31 on the production of IL-13-induced inflammatory cytokines and mucin 5AC by performing western blotting and ELISA. The expression levels of miR-31 were significantly decreased in the nasal mucosa of the AR group compared with those in the control group. Moreover, upregulation of miR-31 markedly attenuated sneezing and nasal rubbing events, reduced nasal eosinophil infiltration and goblet cell hyperplasia, and decreased the levels of OVA-specific IgE and Th2-related cytokines. In addition, subsequent in vitro experiments showed that upregulation of miR-31 inhibited IL-13 receptor α1 chain expression and signal transducer and activator of transcription 6 phosphorylation in NECs. Furthermore, miR-31 suppressed IL-13-induced expression of thymic stromal lymphopoietin, granulocyte-macrophage colony-stimulating factor, eotaxin and mucin 5AC in NECs. In conclusion, these data revealed that miR-31 could ameliorate AR by suppressing IL-13-induced nasal epithelial inflammatory responses, and thus may serve as a novel therapeutic target for AR. [ABSTRACT FROM AUTHOR]