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

Royce, SG; Licciardi, PV; Beh, RC; Bourke, JE; Donovan, C; Hung, A; Khurana, I; Liang, JJ; Maxwell, S; Mazarakis, N; Pitsillou, E; Siow, YY; Snibson, KJ; Tobin, MJ; Ververis, K; Vongsvivut, J; Ziemann, M; Samuel, CS; Tang, MLK; El-Osta, A; Karagiannis, TC

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

Royce, SG Licciardi, PV Beh, RC Bourke, JE Donovan, C

Hung, A Khurana, I Liang, JJ Maxwell, S Mazarakis, N Pitsillou, E Siow, YY Snibson, KJ Tobin, MJ Ververis, K Vongsvivut, J Ziemann, M Samuel, CS Tang, MLK El-Osta, A Karagiannis, TC

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Publisher:: Springer Nature
Publication Type:: Journal Article
Citation:: Cell Mol Life Sci, 2022, 79, (11), pp. 579
Issue Date:: 2022-11-01

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Field	Value	Language
dc.contributor.author	Royce, SG
dc.contributor.author	Licciardi, PV
dc.contributor.author	Beh, RC
dc.contributor.author	Bourke, JE
dc.contributor.author	Donovan, C https://orcid.org/0000-0003-4558-329X
dc.contributor.author	Hung, A
dc.contributor.author	Khurana, I
dc.contributor.author	Liang, JJ
dc.contributor.author	Maxwell, S
dc.contributor.author	Mazarakis, N
dc.contributor.author	Pitsillou, E
dc.contributor.author	Siow, YY
dc.contributor.author	Snibson, KJ
dc.contributor.author	Tobin, MJ
dc.contributor.author	Ververis, K
dc.contributor.author	Vongsvivut, J
dc.contributor.author	Ziemann, M
dc.contributor.author	Samuel, CS
dc.contributor.author	Tang, MLK
dc.contributor.author	El-Osta, A
dc.contributor.author	Karagiannis, TC
dc.date.accessioned	2023-02-06T04:15:45Z
dc.date.available	2022-10-21
dc.date.available	2023-02-06T04:15:45Z
dc.date.issued	2022-11-01
dc.identifier.citation	Cell Mol Life Sci, 2022, 79, (11), pp. 579
dc.identifier.issn	1420-682X
dc.identifier.issn	1420-9071
dc.identifier.uri	http://hdl.handle.net/10453/165936
dc.description.abstract	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.
dc.format	Electronic
dc.language	eng
dc.publisher	Springer Nature
dc.relation.ispartof	Cell Mol Life Sci
dc.relation.isbasedon	10.1007/s00018-022-04609-3
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	0601 Biochemistry and Cell Biology, 0606 Physiology, 1103 Clinical Sciences
dc.subject.classification	Biochemistry & Molecular Biology
dc.subject.mesh	Mice
dc.subject.mesh	Humans
dc.subject.mesh	Animals
dc.subject.mesh	Antioxidants
dc.subject.mesh	Leukocytes, Mononuclear
dc.subject.mesh	Hypersensitivity
dc.subject.mesh	Ovalbumin
dc.subject.mesh	Epigenesis, Genetic
dc.subject.mesh	Anti-Inflammatory Agents
dc.subject.mesh	Leukocytes, Mononuclear
dc.subject.mesh	Animals
dc.subject.mesh	Humans
dc.subject.mesh	Mice
dc.subject.mesh	Hypersensitivity
dc.subject.mesh	Ovalbumin
dc.subject.mesh	Anti-Inflammatory Agents
dc.subject.mesh	Antioxidants
dc.subject.mesh	Epigenesis, Genetic
dc.subject.mesh	Mice
dc.subject.mesh	Humans
dc.subject.mesh	Animals
dc.subject.mesh	Antioxidants
dc.subject.mesh	Leukocytes, Mononuclear
dc.subject.mesh	Hypersensitivity
dc.subject.mesh	Ovalbumin
dc.subject.mesh	Epigenesis, Genetic
dc.subject.mesh	Anti-Inflammatory Agents
dc.title	Sulforaphane prevents and reverses allergic airways disease in mice via anti-inflammatory, antioxidant, and epigenetic mechanisms.
dc.type	Journal Article
utslib.citation.volume	79
utslib.location.activity	Switzerland
utslib.for	0601 Biochemistry and Cell Biology
utslib.for	0606 Physiology
utslib.for	1103 Clinical Sciences
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
utslib.copyright.status	closed_access	*
dc.date.updated	2023-02-06T04:15:43Z
pubs.issue	11
pubs.publication-status	Published online
pubs.volume	79
utslib.citation.issue	11

Abstract:

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.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/165936