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

Autor: Royce SG; Epigenomic Medicine Laboratory, Department of Diabetes, Central Clinical School, Monash University, Alfred Centre, 99 Commercial Road, Melbourne, VIC, 3004, Australia.; Department of Clinical Pathology, University of Melbourne, Parkville, VIC, 3010, Australia.; Department of Pharmacology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3800, Australia.; Infection and Immunity, Murdoch Children's Research Institute, Melbourne, VIC, 3052, Australia., Licciardi PV; Infection and Immunity, Murdoch Children's Research Institute, Melbourne, VIC, 3052, Australia.; Department of Paediatrics, The University of Melbourne, Melbourne, VIC, 3010, Australia., Beh RC; Epigenomic Medicine Laboratory, Department of Diabetes, Central Clinical School, Monash University, Alfred Centre, 99 Commercial Road, Melbourne, VIC, 3004, Australia.; Department of Clinical Pathology, University of Melbourne, Parkville, VIC, 3010, Australia., Bourke JE; Department of Pharmacology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3800, Australia., Donovan C; Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW, 2305, Australia.; Centre for Inflammation, Centenary Institute, Camperdown, NSW, 2050, Australia.; School of Life Sciences, Faculty of Science, University of Technology Sydney, Sydney, NSW, 2007, Australia., Hung A; School of Science, STEM College, RMIT University, VIC, 3001, Australia., Khurana I; Epigenetics in Human Health and Disease Laboratory, Department of Diabetes, Central Clinical School, Monash University, Alfred Centre, 99 Commercial Road, Melbourne, VIC, 3004, Australia., Liang JJ; Epigenomic Medicine Laboratory, Department of Diabetes, Central Clinical School, Monash University, Alfred Centre, 99 Commercial Road, Melbourne, VIC, 3004, Australia.; School of Science, STEM College, RMIT University, VIC, 3001, Australia., Maxwell S; Epigenetics in Human Health and Disease Laboratory, Department of Diabetes, Central Clinical School, Monash University, Alfred Centre, 99 Commercial Road, Melbourne, VIC, 3004, Australia., Mazarakis N; Epigenomic Medicine Laboratory, Department of Diabetes, Central Clinical School, Monash University, Alfred Centre, 99 Commercial Road, Melbourne, VIC, 3004, Australia.; Infection and Immunity, Murdoch Children's Research Institute, Melbourne, VIC, 3052, Australia.; Department of Paediatrics, The University of Melbourne, Melbourne, VIC, 3010, Australia.; Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Parkville, VIC, 3010, Australia., Pitsillou E; Epigenomic Medicine Laboratory, Department of Diabetes, Central Clinical School, Monash University, Alfred Centre, 99 Commercial Road, Melbourne, VIC, 3004, Australia.; School of Science, STEM College, RMIT University, VIC, 3001, Australia., Siow YY; Epigenomic Medicine Laboratory, Department of Diabetes, Central Clinical School, Monash University, Alfred Centre, 99 Commercial Road, Melbourne, VIC, 3004, Australia., Snibson KJ; Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Parkville, VIC, 3010, Australia., Tobin MJ; ANSTO-Australian Synchrotron, Clayton, VIC, 3168, Australia., Ververis K; Epigenomic Medicine Laboratory, Department of Diabetes, Central Clinical School, Monash University, Alfred Centre, 99 Commercial Road, Melbourne, VIC, 3004, Australia.; Department of Clinical Pathology, University of Melbourne, Parkville, VIC, 3010, Australia., Vongsvivut J; ANSTO-Australian Synchrotron, Clayton, VIC, 3168, Australia., Ziemann M; Epigenetics in Human Health and Disease Laboratory, Department of Diabetes, Central Clinical School, Monash University, Alfred Centre, 99 Commercial Road, Melbourne, VIC, 3004, Australia.; School of Life and Environmental Sciences, Deakin University, Waurn Ponds, Warrnambool, VIC, 3216, Australia., Samuel CS; Cardiovascular Disease Program, Monash Biomedicine Discovery Institute and Department of Pharmacology, Monash University, Clayton, VIC, 3800, Australia., Tang MLK; Department of Paediatrics, The University of Melbourne, Melbourne, VIC, 3010, Australia.; Population Allergy Group, Murdoch Children's Research Institute, Parkville, VIC, 3052, Australia.; Department of Allergy and Immunology, Royal Children's Hospital, Parkville, VIC, 3052, Australia., El-Osta A; Epigenetics in Human Health and Disease Laboratory, Department of Diabetes, Central Clinical School, Monash University, Alfred Centre, 99 Commercial Road, Melbourne, VIC, 3004, Australia., Karagiannis TC; Epigenomic Medicine Laboratory, Department of Diabetes, Central Clinical School, Monash University, Alfred Centre, 99 Commercial Road, Melbourne, VIC, 3004, Australia. karat@unimelb.edu.au.; Department of Clinical Pathology, University of Melbourne, Parkville, VIC, 3010, Australia. karat@unimelb.edu.au.
Jazyk: angličtina
Zdroj: Cellular and molecular life sciences : CMLS [Cell Mol Life Sci] 2022 Nov 01; Vol. 79 (11), pp. 579. Date of Electronic Publication: 2022 Nov 01.
DOI: 10.1007/s00018-022-04609-3
Abstrakt: 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.
(© 2022. Crown.)
Databáze: MEDLINE
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