Zonula occludens and nasal epithelial barrier integrity in allergic rhinitis

Abstract

Allergic rhinitis (AR) is a common disease affecting 400 million of the population worldwide. Nasal epithelial cells form a barrier against the invasion of environmental pathogens. These nasal epithelial cells are connected together by tight junction (TJ) proteins including zonula occludens-1 (ZO-1), ZO-2 and ZO-3. Impairment of ZO proteins are observed in AR patients whereby dysfunction of ZOs allows allergens to pass the nasal passage into the subepithelium causing AR development. In this review, we discuss ZO proteins and their impairment leading to AR, regulation of their expression by Th1 cytokines (i.e., IL-2, TNF-α and IFN-γ), Th2 cytokines (i.e., IL-4 and IL-13) and histone deacetylases (i.e., HDAC1 and HDAC2). These findings are pivotal for future development of targeted therapies by restoring ZO protein expression and improving nasal epithelial barrier integrity in AR patients.

Potential effect of fish oil to preserve expression of cell cycle and tight junction regulating genes in colon after di-isononyl phthalate ingestion in albino Wistar rats

“…In the current results, DIP-group showed a nonsignificant change of gene expression responsible for tight junctions (ZO-1, ZO-2, CLDN1, CLDN4, OCLN) 25 associated with a significant decrease of ZO-3 gene expression if compared to C-group which may allow pathogens to penetrate into colon wall causing further inflammation. 26 On the other hand, these gene expressions were comparable in both C-group and DIP-FO-group. Which could prove the ability of FO to maintain the tight junction integrity between colon cells, enhancing its immunity role.…”

Nasal Epithelial Barrier Integrity and Tight Junctions Disruption in Allergic Rhinitis: Overview and Pathogenic Insights

“…Differential expression of TJ molecules has also been found in distinct inflammatory phenotypes of allergic airway inflammation in mice compared to controls (8). These findings suggest that TJs disruption plays causative roles in the development of allergy through increased exposure of nasal tissues to environmental allergens (9). In this review, we present and discuss the association of TJs disruption in AR, as well as regulation of TJs expression by epigenetic changes, neuroimmune interaction, epithelium-derived cytokines, T helper 2 (Th2) cytokines and innate lymphoid cells (ILCs).…”

“…Lastly, epigenetic regulation can occur via histone posttranslational modifications (PTMs) such as acetylation (123). Histone deacetylases (HDACs), an enzymes responsible for removing acetyl group from lysine residues of target proteins and block genes transcription by allowing DNA to be wrapped by histones and promote chromatin condensation (9,126,127). HDACs are associated with defects in epithelial barrier of AR (128).…”

Oxidative Stress and Antioxidant Pathway in Allergic Rhinitis

“…In the pathogenesis of allergic rhinitis, antigen presentation by dendritic cells is the first step in allergen sensitization. It has been reported that physical epithelial barrier dysfunction in the nasal epithelium may contribute to the uptake of allergens and harmful exogenous particles in allergic rhinitis ( Figure 3 c) [ 84 , 85 , 86 ]. In allergic rhinitis patients with house dust mite allergy, epithelial barrier function impairment was found with increased epithelial permeability and altered occludin and zonula occludens (ZO)-1 expression [ 87 ].…”

“…The nasal epithelial cell barrier is made up of cell-to-cell tight junctions, which are formed with scaffold adaptor proteins ZO-1, ZO-2, and ZO-3 and integral membrane proteins such as occludin [ 86 , 88 ]. In a recent study, human sinonasal epithelial cells were used to study epithelial cell barrier function under allergic conditions [ 89 ].…”