AhR Causes the Release of Proinflammatory Cytokines and Chemokines and Airway Epithelial Barrier Dysfunction in Allergic Rhinitis via Upregulating SERPINB2.

Introduction: Allergic rhinitis (AR) remains a kind of nasal hypersensitivity illness with a considerable surge in incidence across the globe. Plasminogen activator inhibitor type 2 (SERPINB2) is an inflammatory mediator that can also be activated by aryl hydrocarbon receptor (AhR), a nuclear receptor that modulates the response to environmental stimuli. This work was devoted to the investigation into the role of SERPINB2 in AR and its relationship with AhR.

Methods: In human nasal epithelial cells (HNEpCs) stimulated with interleukin-4 (IL-4) or histamine, an enzyme-linked immunosorbent assay was adopted for quantifying proinflammatory cytokines and chemokines. Epithelial barrier function was assessed by transepithelial electrical resistance (TER). Western blot and immunofluorescence staining evaluated tight junction proteins. Reverse transcription-quantitative PCR and Western blot determined SERPINB2 and AhR expressions.

Results: The release of proinflammatory cytokines and chemokines was aggravated, TER value was reduced and the expressions of tight junction proteins were downregulated in HNEpCs when induced by IL-4 or histamine. SERPINB2 and AhR were both overexpressed and SERPINB2 depletion relieved inflammatory response and preserved epithelial barrier function in IL-4- or histamine-treated HNEpCs. Besides, AhR knockdown decreased SERPINB2 expression and SERPINB2 upregulation reverted the protective role of AhR silencing in the inflammatory response and epithelial barrier dysfunction in HNEpCs in response to IL-4 or histamine.

Conclusion: Collectively, AhR might activate SERPINB2 to exacerbate inflammation and airway epithelial barrier dysfunction in AR.