期刊
PHARMACEUTICALS
卷 15, 期 8, 页码 -出版社
MDPI
DOI: 10.3390/ph15080966
关键词
antioxidant; epigenetic; histone; inflammation; macrophages; (R)-sulforaphane; spleen cells
资金
- Ministerio de Ciencia, Innovacion y Universidades [PID2019-104767RB-I00/AEI/10.13039/501100011033]
- Consejeria de Transformacion Economica, Industria, Conocimiento y Universidad, Junta de Andalucia [P20-01171, FQM-102]
- Consejeria de Economia, Conocimiento, Empresas y Universidad, Junta de Andalucia [2021/CTS-259, CTS-259]
This study found that the natural enantiomer (R)-Sulforaphane (SFN) could modulate the immune response in LPS-stimulated murine macrophages and spleen cells by inhibiting oxidative stress and inflammatory factors. The effects of (R)-SFN on immune modulation may be mediated through various signaling pathways and epigenetic modifications. These findings suggest that (R)-SFN could be a promising compound for the management of immunoinflammatory diseases.
The aim of this study was to explore the immunomodulatory effects of the natural enantiomer (R)-Sulforaphane (SFN) and the possible signaling pathways involved in an ex vivo model of LPS-stimulated murine peritoneal macrophages. Furthermore, we studied the epigenetic changes induced by (R)-SFN as well as the post-translational modifications of histone H3 (H3K9me3 and H3K18ac) in relation to the production of cytokines in murine splenocytes after LPS stimulation. (R)-SFN was able to modulate the inflammatory response and oxidative stress induced by LPS stimulation in murine peritoneal macrophages through the inhibition of reactive oxygen species (ROS), nitric oxide (NO) and cytokine (IL-1 beta, IL-6, IL-17, IL-18 and TNF-alpha) production by down-regulating the expression of pro-inflammatory enzymes (iNOS, COX-2 and mPGES-1). We also found that activation of the Nrf-2/HO-1 axis and inhibition of the JAK2/STAT-3, MAPK, canonical and non-canonical inflammasome signaling pathways could have been responsible for the immunomodulatory effects of (R)-SFN. Furthermore, (R)-SFN modulated epigenetic modifications through histone methylation (H3K9me3) and deacetylation (H3K18ac) in LPS-activated spleen cells. Collectively, our results suggest that (R)-SFN could be a promising epinutraceutical compound for the management of immunoinflammatory diseases.
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