Compound D from Zingiber cassumunar Roxb. attenuated type 2 inflammatory cytokine-induced tight junction disruption in airway epithelial cells.

Abstract

Barrier disruption in the airway mucosae has been implicated in allergic type 2 inflammatory diseases such as allergic rhinitis and asthma. Zingiber cassumunar Roxb. has long been used in traditional medicine to treat allergic diseases. The active compound, namely compound D, has proven anti-inflammatory benefits. However, the effect of compound D on allergic inflammation remains unclear. This study aimed to investigate the protective effects of compound D on allergic inflammation-induced barrier disruption. Type 2 cytokine (IL-4 and IL-13)-exposed 16HBE human bronchial epithelial cells were treated with compound D. After 24, 48, and 72 h, cytotoxicity, epithelial integrity, and tight junction (TJ) disruption were determined by viability assays, transepithelial electrical resistance measurement, and immunofluorescence staining, respectively. Moreover, the mechanism of action of compound D was investigated by western blotting. Compound D (100 and 200 µM) prevented IL-4/IL-13-induced barrier disruption at 24 and 48 h with no effect on cell viability. Compound D rescued the localization of ZO-1 to pericellular areas, and the barrier-protective effect of compound D was mediated by inhibiting STAT6 signaling. Compound D can suppress IL-4/IL-13-induced epithelial inflammation and TJ disruption through STAT6 inhibition. The agent is a promising candidate for therapeutic or adjunctive treatment of type 2 inflammation-associated diseases, including asthma.