Inhibition of TRPV1 attenuates innate nasal epithelial responses via NF-κB signaling pathway in allergic rhinitis

Nasal epithelial cells initiate innate responses to allergens by releasing IL-1 family cytokines, such as IL-33, and disrupting the mucosal barrier. TRPV1 has gained increasing recognition for its role in immune modulation in allergic conditions. This study aimed to elucidate the mechanisms by which epithelial cells detect allergens and explore the pivotal role of TRPV1 in regulating innate nasal epithelial responses.

To identify TRPV1-related genes and pathways, the GSE167225 dataset was analyzed. To validate TRPV1 expression, clinical data and nasal tissues from 34 patients with AR and 13 controls were collected. To further investigate its mechanisms, OVA-sensitized C57BL/6 mice were exposed to the TRPV1 antagonist SB-705498, and TRPV1 knockout mice were utilized. Primary human nasal epithelial cells were used for in vitro experiments, and various assays, including reverse transcription polymerase chain reaction(RT-PCR), western blotting(WB), and others, were performed to assess gene expression and signaling pathways.

Bioinformatics and clinical analysis revealed elevated TRPV1 expression in patients with AR, positively correlated with nasal itching and sneezing severity(R = 0.6493, P < 0.001; R = 0.4906, P < 0.001). In vivo, SB-705498 and TRPV1 ablation significantly alleviated allergy symptoms, reduced allergen-induced IL-33 release, and prevented disruption of tight junction protein occludin in murine models. In vitro, TRPV1 antagonism suppressed capsaicin-induced calcium influx, NF-κB activation, and IL-33 overexpression.

Allergen exposure enhances the secretion of IL-33 in hNECs via the TRPV1-NF-κB pathway, thus compromising epithelial tight junction integrity. Inhibition of TRPV1 can attenuate the effects of allergen-induced innate nasal epithelial responses. Our study offers novel insights into the potential therapeutic targeting of TRPV1 in AR.