J Rhinol.  2023 Nov;30(3):161-166. 10.18787/jr.2023.00062.

The Relationship Between Zonulin and Asthma: A Mouse Model Study

• Hong JP
• Kang SH
• Chu J
• Byeon SJ
• Lee H
• Choi JH
• Lee KC
• Hong SJ

• KMID: 2548194
• DOI: http://doi.org/10.18787/jr.2023.00062

Abstract

Background and Objectives
Zonulin is a human protein that regulates intercellular tight junctions and increases the permeability of the intestinal epithelium. In light of the increasing focus on zonulin’s role in numerous chronic inflammatory diseases, this study aimed to investigate whether differences exist in serum zonulin levels and bronchial epithelium zonulin expression in vivo between asthma and normal groups, using a mouse model.
Methods
Sixteen mice were utilized in this study, divided evenly between the normal and asthma groups. Serum zonulin levels, the expression of zonulin antibody in the bronchial epithelium, and serum cytokine levels were evaluated in both groups. Enzyme-linked immunosorbent assay and RNA in situ hybridization were utilized for the analysis.
Results
The asthma group exhibited significantly higher levels of serum zonulin. High zonulin antibody expression was also observed in the bronchial epithelium of the asthma group. Given that our mouse model demonstrated a significant difference in interleukin (IL)-4 and IL-6 between the normal and asthma groups, zonulin may be associated not only with type 2 responses but also with various subtypes of asthma. Further studies are required to investigate this relationship in greater detail.
Conclusion
Zonulin may play a role in the complex pathophysiology of asthma and could serve as a biomarker in various asthma-related situations.

Keyword

Zonulin; Asthma; Biomarker

Figure

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  Fig. 1. Schematic presentation of the preparation process of OVA/LPS induced asthma disease model. IgE levels were measured to confirm asthma development (***p<0.001). OVA, ovalbumin; LPS, lipopolysaccharide; IgE, immunoglobulin E.

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  Fig. 2. Serum zonulin levels in the normal and asthma groups. A bar graph shows the significant difference (p=0.042) in serum zonulin levels, measured using ELISA, in normal and asthmatic mouse. An asterisk (*p<0.05) in the graph represents significant difference. ELISA, enzyme-linked immunosorbent assay.

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  Fig. 3. Zonulin antibody expression in the bronchial epithelium of asthmatic mice. A: Zonulin antibody expression in the bronchial epithelium in our asthma model. The zonulin antibody is marked by brown color (black arrows) in the bronchial epithelium (red circle). The RNA ISH technique was utilized for zonulin antibody identification. B: Representative image of zonulin antibody analysis using the RNA ISH technique. Antibody expression in the bronchial epithelium is highlighted in a red circle. This images were taken under 400× magnification. ISH, in situ hybridization.

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  Fig. 4. Serum cytokine levels in the normal and asthma groups. There were significant differences in IL-4 (p=0.019) and IL-6 (p=0.038). Asterisks (*p<0.05) in the graph represent significant differences. IL, interleukin; TNF, tumor necrosis factor.

Reference

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