Molecular hydrogen alleviates asthma through inhibiting IL-33/ILC2 axis.

Abstract

Using an OVA-sensitized asthmatic mouse model and a house dust mite (HDM)-stimulated 16HBE bronchial epithelial cell model, this study examined the effects of hydrogen/oxygen gas mixture on type II airway inflammation. In OVA-challenged mice, serum and bronchoalveolar lavage fluid concentrations of IL-33 and other type II cytokines were markedly elevated; hydrogen administration significantly reduced these levels. NF-κB (p65) and ST2 expression were upregulated by OVA and downregulated by hydrogen. The ILC2 population expanded in asthmatic mice was substantially reduced following hydrogen exposure. Airway epithelial junction proteins E-cadherin and ZO-1, diminished in asthmatic mice, were restored by hydrogen. In HDM-treated 16HBE cells, hydrogen attenuated apoptosis, suppressed IL-33 and ST2 upregulation, and reduced IL-33 promoter activity as measured by dual-luciferase assay. miRNA array profiling identified a distinct set of differentially expressed miRNAs in HDM-exposed cells that were modulated by hydrogen co-treatment. Collectively, these findings indicate that molecular hydrogen suppresses allergen-driven type II inflammation through the IL-33/ILC2 axis.

Mechanism

Molecular hydrogen suppresses NF-κB (p65) activation, thereby reducing IL-33 promoter activity and ST2 expression, which in turn limits ILC2 expansion and downstream type II inflammatory cytokine production.