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Epigenetic modulation of TLR4 expression by sulforaphane increases anti-inflammatory capacity in porcine monocyte-derived dendritic cells

Qu, X., Neuhoff, C., Cinar, M.U., Pröll, M., Tholen, E., Tesfaye, D., Hölker, M., Schellander, K. and Uddin, M.J. (2021) Epigenetic modulation of TLR4 expression by sulforaphane increases anti-inflammatory capacity in porcine monocyte-derived dendritic cells. Biology, 10 (6). p. 490.

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Abstract

Inflammation is regulated by epigenetic modifications, including DNA methylation and histone acetylation. Sulforaphane (SFN), a histone deacetylase (HDAC) inhibitor, is also a potent immunomodulatory agent, but its anti-inflammatory functions through epigenetic modifications remain unclear. Therefore, this study aimed to investigate the epigenetic effects of SFN in maintaining the immunomodulatory homeostasis of innate immunity during acute inflammation. For this purpose, SFN-induced epigenetic changes and expression levels of immune-related genes in response to lipopolysaccharide (LPS) stimulation of monocyte-derived dendritic cells (moDCs) were analyzed. These results demonstrated that SFN inhibited HDAC activity and caused histone H3 and H4 acetylation. SFN treatment also induced DNA demethylation in the promoter region of the MHC-SLA1 gene, resulting in the upregulation of Toll-like receptor 4 (TLR4), MHC-SLA1, and inflammatory cytokines’ expression at 6 h of LPS stimulation. Moreover, the protein levels of cytokines in the cell culture supernatants were significantly inhibited by SFN pre-treatment followed by LPS stimulation in a time-dependent manner, suggesting that inhibition of HDAC activity and DNA methylation by SFN may restrict the excessive inflammatory cytokine availability in the extracellular environment. We postulate that SFN may exert a protective and anti-inflammatory function by epigenetically influencing signaling pathways in experimental conditions employing porcine moDCs.

Item Type: Journal Article
Murdoch Affiliation(s): Veterinary Medicine
Publisher: MDPI
Copyright: © 2021 The Authors.
URI: http://researchrepository.murdoch.edu.au/id/eprint/61265
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