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Immunopharmacol Immunotoxicol ; 43(6): 813-824, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34694946

RESUMO

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.


Assuntos
Sobrevivência Celular/efeitos dos fármacos , Pyroglyphidae/metabolismo , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/metabolismo , Sesquiterpenos/farmacologia , Animais , Linhagem Celular , Linhagem Celular Transformada , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Humanos , Lactente , Masculino , Pyroglyphidae/imunologia , Mucosa Respiratória/imunologia
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