Compound D from Zingiber cassumunar Roxb. attenuatedtype 2 inflammatory cytokine-induced tight junction disruptionin airway epithelial cells
Orapan Poachanukoon,1,2,3,† Pasistha Termworasin,1,† Phuntila Tharabenjasin,4 Thaweephol Dechatiwongse Na Ayudhya,2 Aekkacha Moonwiriyakit5
Affiliations:
1 Center of Excellence for Allergy, Asthma and Pulmonary Disease, Thammasat University, Pathum Thani, Thailand
2 Medicinal Herb Research Unit for Asthma, Thammasat University, Pathum Thani, Thailand
3 Division of Allergy and Immunology, Department of Pediatrics, Faculty of Medicine, Thammasat University, Pathum Thani, Thailand
4 Chulabhorn International College of Medicine, Thammasat University, Pathum Thani, Thailand
5 Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Samut Prakarn, Thailand
†The first and second authors contributed equally to the manuscript
Abstract
Background: 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.
Objective: This study aimed to investigate the protective effects of compound D on allergic inflammation-induced barrier disruption.
Methods: 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.
Results: 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.
Conclusions: 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.
Key words: Zingiber cassumunar Roxb, asthma, allergic inflammation, tight junction, airway epithelial cells