Journal Article

Sulforaphane prevents and reverses allergic airways disease in mice via anti-inflammatory, antioxidant, and epigenetic mechanisms

Bourke, Jane E., Donovan, Chantal, Khurana, Ishant, Siow, Ya Yun, Snibson, Kenneth J., Mazarakis, Nadia, El-Osta, Assam, Karagiannis, Tom C., Vongsvivut, Jitraporn, Liang, Julia J., Tang, Mimi L. K., Pitsillou, Eleni, Maxwell, Scott, Ziemann, Mark, Tobin, Mark J., Hung, Andrew, Licciardi, Paul V., Royce, Simon G., Beh, Raymond C., Ververis, Katherine, Samuel, Chrishan S.

2022

Overview

Sulforaphane has been investigated in human pathologies and preclinical models of airway diseases. To provide further mechanistic insights, we explored L-sulforaphane (LSF) in the ovalbumin (OVA)-induced chronic allergic airways murine model, with key hallmarks of asthma. Histological analysis indicated that LSF prevented or reversed OVA-induced epithelial thickening, collagen deposition, goblet cell metaplasia, and inflammation. Well-known antioxidant and anti-inflammatory mechanisms contribute to the beneficial effects of LSF. Fourier transform infrared microspectroscopy revealed altered composition of macromolecules, following OVA sensitization, which were restored by LSF. RNA sequencing in human peripheral blood mononuclear cells highlighted the anti-inflammatory signature of LSF. Findings indicated that LSF may alter gene expression via an epigenetic mechanism which involves regulation of protein acetylation status. LSF resulted in histone and α-tubulin hyperacetylation in vivo, and cellular and enzymatic assays indicated decreased expression and modest histone deacetylase (HDAC) inhibition activity, in comparison with the well-known pan-HDAC inhibitor suberoylanilide hydroxamic acid (SAHA). Molecular modeling confirmed interaction of LSF and LSF metabolites with the catalytic domain of metal-dependent HDAC enzymes. More generally, this study confirmed known mechanisms and identified potential epigenetic pathways accounting for the protective effects and provide support for the potential clinical utility of LSF in allergic airways disease.

• Publisher: Springer International Publishing,Springer Nature B.V
• Subject: Acetylation / active sites / Animal models / Animals / Anti-Inflammatory Agents / Antioxidants / Asthma / Biochemistry / Biomedical and Life Sciences / Biomedicine / Cell Biology / Collagen / Epigenesis, Genetic / Epigenetics / epithelium / Fourier transform infrared spectroscopy / Fourier transforms / Gene expression / Gene sequencing / histology / Histone deacetylase / Histones / Humans / Hydroxamic acid / Hypersensitivity / Inflammation / Leukocytes, Mononuclear / Life Sciences / Macromolecules / Metabolites / Metaplasia / Mice / Molecular modelling / Original / Original Article / Ovalbumin / Peripheral blood mononuclear cells / Respiratory tract diseases / RNA / Sulforaphane / Thickening / Tubulin