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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-? and IFN-?), 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.

SUBMITTER: Siti Sarah CO

PROVIDER: S-EPMC7476493 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Zonula occludens and nasal epithelial barrier integrity in allergic rhinitis.

Siti Sarah Che Othman CO Md Shukri Norasnieda N Mohd Ashari Noor Suryani NS Wong Kah Keng KK

PeerJ 20200904

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 revi ...[more]

PMID: 32953271

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Project description:BACKGROUND:Anisakis spp. are nematode parasites found in a wide range of marine organisms. Human beings may accidentally become infected, showing the symptoms of anisakiasis and allergic responses. There has been evidence of increased intestinal permeability in A. simplex-sensitized subjects and that specific IgE titres increase in some allergic patients when fishery products are re-introduced into their diet. The aims of this work were to study the effect of A. simplex crude extract on the intestinal integrity and permeability by using Caco-2 cell monolayer. To analyse the capacity of Ani s 4 allergen to cross the epithelial barrier. METHODOLOGY/PRINCIPAL FINDINGS:Cellular bioenergetics, transepithelial electrical resistance, viability, permeability, reactive oxygen species generation and immunofluorescent staining of tight junction proteins were analysed. A. simplex crude extract compromises the Caco-2 cell monolayer integrity in a dose-dependent manner. This effect is detected at 1 hour of culture and integrity is recovered after 24 hours of culture. The epithelial barrier disruption is accompanied by an increase in paracellular permeability and reactive oxygen species production and by a delocalization of occludin and zonula occludens-1. Finally, Ani s 4, a thermostable and resistant to digestion allergen with cystatin activity, is able to cross the epithelial barrier in Caco-2 monolayer and reach a cumulative mean percentage of 22.7% of total concentration in the basolateral side after 24 hours of culture. CONCLUSIONS/SIGNIFICANCE:Our results demonstrate that A. simplex induces an early and reversible alteration of integrity and permeability of Caco-2 cell monolayer and that an underlying mechanism of this effect would involve the oxidative stress and disruption of epithelial tight junctions. Additionally, it has been shown that Ani s 4 allergen is able to cross the epithelial barrier. These findings could explain the increased intestinal permeability observed in Anisakis-sensitized patients, the changes over time in IgE sensitization to A. simplex allergens, and the specific IgE persistence in Anisakis allergy.

Project description:IntroductionAlthough recent studies have shown that the human microbiome is involved in the pathogenesis of allergic diseases, the impact of microbiota on allergic rhinitis (AR) and non-allergic rhinitis (nAR) has not been elucidated. The aim of this study was to investigate the differences in the composition of the nasal flora in patients with AR and nAR and their role in the pathogenesis.MethodFrom February to September 2022, 35 AR patients and 35 nAR patients admitted to Harbin Medical University's Second Affiliated Hospital, as well as 20 healthy subjects who underwent physical examination during the same period, were subjected to 16SrDNA and metagenomic sequencing of nasal flora.ResultsThe microbiota composition of the three groups of study subjects differs significantly. The relative abundance of Vibrio vulnificus and Acinetobacter baumanni in the nasal cavity of AR patients was significantly higher when compared to nAR patients, while the relative abundance of Lactobacillus murinus, Lactobacillus iners, Proteobacteria, Pseudomonadales, and Escherichia coli was lower. In addition, Lactobacillus murinus and Lacttobacillus kunkeei were also negatively correlated with IgE, while Lacttobacillus kunkeei was positively correlated with age. The relative distribution of Faecalibacterium was higher in moderate than in severe AR patients. According to KEGG functional enrichment annotation, ICMT(protein-S-isoprenylcysteine O-methyltransferase,ICMT) is an AR microbiota-specific enzyme that plays a role, while glycan biosynthesis and metabolism are more active in AR microbiota. For AR, the model containing Parabacteroides goldstemii, Sutterella-SP-6FBBBBH3, Pseudoalteromonas luteoviolacea, Lachnospiraceae bacterium-615, and Bacteroides coprocola had the highest the area under the curve (AUC), which was 0.9733(95%CI:0.926-1.000) in the constructed random forest prediction model. The largest AUC for nAR is 0.984(95%CI:0.949-1.000) for the model containing Pseudomonas-SP-LTJR-52, Lachnospiraceae bacterium-615, Prevotella corporis, Anaerococcus vaginalis, and Roseburia inulinivorans.ConclusionIn conclusion, patients with AR and nAR had significantly different microbiota profiles compared to healthy controls. The results suggest that the nasal microbiota may play a key role in the pathogenesis and symptoms of AR and nAR, providing us with new ideas for the treatment of AR and nAR.

Dataset Information

Zonula occludens and nasal epithelial barrier integrity in allergic rhinitis.

Publications

Zonula occludens and nasal epithelial barrier integrity in allergic rhinitis.

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