TAK-242 ameliorates olfactory dysfunction in a mouse model of allergic rhinitis by inhibiting neuroinflammation in the olfactory bulb.

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.