Zerumbone attenuates house dust mite extract-induced epithelial barrier dysfunction in 16HBE14o- cells

Abstract

Context

The airway epithelial barrier can be disrupted by house dust mite (HDM) allergens leading to allergic airway inflammation. Zerumbone, a natural monocyclic sesquiterpene, was previously found to possess anti-asthmatic effect by modulating Th1/Th2 cytokines. However, the protective role of zerumbone on epithelial barrier function remains to be fully explored.

Objective

To investigate the effect of zerumbone on HDM extract-induced airway epithelial barrier dysfunction.

Materials and methods

Human bronchial epithelial cells 16HBE14o- were incubated with 100 μg/mL HDM extract and treated with non-cytotoxic concentrations of zerumbone (6.25 μM, 12.5 μM, and 25 μM) for 24 h. The epithelial junctional integrity and permeability were evaluated through transepithelial electrical resistance (TEER) and fluorescein isothiocynate (FITC)-Dextran permeability assays, respectively. The localization of junctional proteins, occludin and zona occludens (ZO)-1, was studied using immunofluorescence (IF) while the protein expression was measured by western blot.

Results

Zerumbone inhibited changes in junctional integrity (6.25 μM, p ≤ .05; 12.5 μM, p ≤ .001; 25 μM, p ≤ .001) and permeability (6.25 μM, p ≤ .05; 12.5 μM, p ≤ .01; 25 μM, p ≤ .001) triggered by HDM extract in a concentration-dependent manner. This protective effect could be explained by the preservation of occludin (12.5 μM, p ≤ .01 and 25 μM, p ≤ .001) and ZO-1 (12.5 μM, p ≤ .05 and 25 μM, p ≤ .001) localization, rather than the prevention of their cleavage.

Discussion and conclusion

Zerumbone attenuates HDM extract-induced epithelial barrier dysfunction which supports its potential application for the treatment of inflammation-driven airway diseases such as asthma.

Keywords:

• House dust mite
• epithelial barrier dysfunction
• asthma
• tight junction
• zerumbone

Acknowledgements

The researchers thanked the Faculty of Medicine and Health Sciences, Universiti Putra Malaysia for the support given throughout this study.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data used to support the findings in the study are available on reasonable request to the corresponding authors.

Additional information

Funding

This work was supported by Universiti Putra Malaysia under Grant Putra Young Initiative-Universiti Putra Malaysia (IPM-UPM) [GP-IPM/2015/9455600] and Malaysia Toray Science Foundation [Grant No: 6378700]. WR was funded by Universiti Putra Malaysia Graduate Research Fellowship (GRF). JWT was a recipient of MyPhD scholarship under MyBrain15 programme. KYL was funded by Universiti Putra Malaysia Graduate Research Assistantship (GRA).