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IL-4/IL-13 Axis in Allergic Rhinitis: Elevated Serum Cytokines Levels and Inverse Association With Tight Junction Molecules Expression.


ABSTRACT: The IL-4/IL-13 axis is involved in the pathogenesis of allergic rhinitis (AR). In this study, we investigated the serum cytokines levels of IL-4, IL-5, IL-6, and IL-13 in AR patients, and the transcript expression levels of their receptors (i.e. IL4R, IL5RA, IL6R, and IL13RA1) in nasal epithelial cells of AR patients versus non-allergic controls. Nasal epithelial cells and blood samples of non-allergic controls (n = 30) and AR patients (n = 30) were collected to examine mRNA expression and serum cytokines levels, respectively. Bioinformatics analyses of IL-4/IL-13 receptor heterodimer association with tight junction (TJ) and JAK/STAT signaling genes were conducted in a gene expression profiling (GEP) dataset (GSE44037) of AR patients (n = 12) and healthy controls (n = 6). Serum IL-4, IL-5, IL-6 or IL-13 levels, and IL13RA1 transcript expression were significantly higher in AR patients compared with non-allergic controls. IL-4 and IL-13 serum levels were positively correlated with IL13RA1 expression in AR patients but not in non-allergic controls. In the GEP dataset (GSE44037), six TJ (CLDN4, CLDN7, CLDN12, CLDN15, TJP1, and TJP2) genes' expressions were negatively correlated, respectively, with IL-4Rα/IL-13Rα1 heterodimeric receptor expression in AR patients and not in control samples. These six TJ genes contributed to the significant enrichment of tight junction Gene Ontology (GO ID: 0070160). Lastly, STATs DNA binding motif analysis showed that each of these TJ genes contains STATs binding consensus sequence within intronic and intergenic regions. Our results suggest that increased IL-4/IL-13 serum cytokines levels may contribute to decreased TJs expression via IL-4Rα/IL-13Rα1 heterodimeric receptor in nasal epithelium of AR patients.

SUBMITTER: Nur Husna SM 

PROVIDER: S-EPMC8969661 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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IL-4/IL-13 Axis in Allergic Rhinitis: Elevated Serum Cytokines Levels and Inverse Association With Tight Junction Molecules Expression.

Nur Husna Siti Muhamad SM   Md Shukri Norasnieda N   Tuan Sharif Sharifah Emilia SE   Tan Hern Tze Tina HTT   Mohd Ashari Noor Suryani NS   Wong Kah Keng KK  

Frontiers in molecular biosciences 20220317


The IL-4/IL-13 axis is involved in the pathogenesis of allergic rhinitis (AR). In this study, we investigated the serum cytokines levels of IL-4, IL-5, IL-6, and IL-13 in AR patients, and the transcript expression levels of their receptors (<i>i.e. IL4R</i>, <i>IL5RA</i>, <i>IL6R,</i> and <i>IL13RA1</i>) in nasal epithelial cells of AR patients <i>versus</i> non-allergic controls. Nasal epithelial cells and blood samples of non-allergic controls (<i>n</i> = 30) and AR patients (<i>n</i> = 30) we  ...[more]

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