Publication: Investigating tight junction proteinrelated regulation of nasal epithelial barrier integrity in allergic rhinitis patients and non-allergic individuals
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Date
2023-08
Authors
Othman, Siti Sarah Che
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Abstract
Allergic rhinitis (AR) is an allergic disease affecting a huge population
worldwide. Despite not being fatal, it has a significant impact on the quality of life.
The nasal epithelial barrier is considered crucial for the first line of defence in the
upper airway as it protects the host immune system from exposure to allergens.
Defective tight junctions (TJs) contribute to nasal epithelial barrier dysfunction in
moderate-severe AR patients. However, the association of nasal epithelial TJs, zonula
occludens (ZO) proteins and histone deacetylases (HDACs) with the demographical,
clinical and environmental characteristics of AR patients remains unclear. In this
study, we aimed to investigate the mRNA expression of ZO-1, ZO-2, ZO-3, HDAC1
and HDAC2 in nasal epithelial cells of house dust mites (HDMs)-sensitised AR
patients compared to non-allergic controls. We also examine the association between
ZO-1, ZO-2, ZO-3, HDAC1 and HDAC2 levels in nasal epithelial cells with the
demographical, clinical and environmental parameters of AR patients and non-allergic
controls. The recruited subjects consisted of 28 AR patients and 28 non-allergic
controls. A Skin prick test (SPT) was performed on the subjects to determine whether
they were allergically sensitised to either one of the HDM allergens. We started this
study by collecting nasal epithelial cell samples from all the subjects. The RNA
samples were reverse transcribed into cDNAs for measurement of ZO-1, ZO-2, ZO-3,
HDAC1 and HDAC2 expression levels by quantitative real-time polymerase chain
reaction (qRT-PCR). The mRNA expression of ZO-1 was significantly decreased in AR patients compared to non-allergic controls (p=0.010). No significant difference
was observed in the expression levels of ZO-2, ZO-3, HDAC1 and HDAC2 in AR
patients compared to non-allergic controls. However, we found a significant
association of higher HDAC2 levels in AR patients sensitised to Dermatophagoides
farinae (D. farinae) (p=0.041). We also found significant associations of higher
HDAC2 levels in AR patients with lower frequency of changing bedsheet (p=0.043).
Higher expression of ZO-2 was observed in AR patients who had pets (p=0.007). In
conclusion, our data indicated that ZO-1 expression was lower in AR patients,
contributing to decreased nasal epithelial barrier integrity. In addition, we also
demonstrated a correlation between the mRNA expression of ZO-2 and HDAC2 in
nasal epithelial cells with specific environmental parameters. Furthermore, the
presence of allergens in the bedsheet also leads to an increase in HDAC2 expression,
which may affect ZOs expression in nasal epithelial barrier. Targeting the nasal
epithelial barrier by restoring ZO-1 expression may be a promising therapeutic
approach for AR patients.