Elevated S100A8 in nasal mucosa correlates with epithelial barrier dysfunction in allergic rhinitis

• S100A8 is upregulated in AR and correlates with disease severity. • S100A8 negatively regulates tight junction proteins in the nasal epithelium. • Knocking down S100A8 restores the barrier integrity in HDM-exposed HNECs. Epithelial barrier dysfunction is central to the pathogenesis of Allergic Rhinitis (AR), yet its molecular mechanisms remain unclear. S100A8 is implicated in epithelial barrier disruption, but its role in AR is not fully understood. This study aimed to investigate S100A8 expression in AR and its association with barrier dysfunction. Nasal mucosal tissues were collected from 30 AR patients and 30 Healthy Controls (HCs). Expression levels of S100A8 and tight junction proteins (ZO-1, E-cadherin, occludin) were assessed by Immunofluorescence (IF), Western Blot (WB), and RT-qPCR. Correlation analysis was performed to evaluate the relationship between S100A8 and tight junction markers. Human Nasal Epithelial Cells (HNECs) from HCs were stimulated with House Dust Mite (HDM) extracts, and S100A8 expression was silenced using siRNA to assess its role in HDM-induced barrier disruption. WB and RT-qPCR results showed that the expression of S100A8 was significantly enhanced in nasal mucosal samples of AR patients compared to the HC group. S100A8 mRNA level was significantly elevated, and its level was positively correlated with the Visual Analog Scores (VAS) and total nasal symptom scores (TNSS) of the patients. Moreover, IF further confirmed that S100A8 was enhanced in the AR group, and mainly localised in the nasal epithelium. The expression of ZO-1, E-cadherin, and occludin was markedly reduced in AR patients and showed a negative correlation with S100A8 levels. In vitro, HDM stimulation of HNECs led to a dose- and time-dependent increase in S100A8 expression, along with reduced levels of tight junction proteins. Silencing S100A8 via siRNA significantly restored tight junction protein expression, indicating that S100A8 inhibition may help preserve nasal epithelial barrier integrity. S100A8 is upregulated in AR and associated with disease severity and epithelial barrier dysfunction. Targeting S100A8 may offer a therapeutic strategy to preserve nasal barrier integrity in AR. Level 3.