1. Sulforaphane and its methylcarbonyl analogs inhibit the LPS-stimulated inflammatory response in human monocytes through modulating cytokine production, suppressing chemotactic migration and phagocytosis in a NF-κB- and MAPK-dependent manner.
- Author
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Reddy SA, Shelar SB, Dang TM, Lee BN, Yang H, Ong SM, Ng HL, Chui WK, Wong SC, and Chew EH
- Subjects
- Animals, Cell Line, Cell Movement drug effects, Cell Survival drug effects, Cells, Cultured, Cyclooxygenase 2 genetics, Cyclooxygenase 2 metabolism, Cytokines genetics, Cytokines metabolism, Dinoprostone metabolism, HEK293 Cells, Humans, I-kappa B Kinase metabolism, Lipopolysaccharides, Matrix Metalloproteinase 9 metabolism, Mice, Mitogen-Activated Protein Kinases metabolism, Monocytes metabolism, Monocytes physiology, NF-kappa B metabolism, Nitric Oxide Synthase Type II genetics, Nitric Oxide Synthase Type II metabolism, Nitrites metabolism, Phagocytosis drug effects, Sulfoxides, Anti-Inflammatory Agents pharmacology, Isothiocyanates pharmacology, Monocytes drug effects
- Abstract
Sulforaphane [SF; 1-isothiocyanato-4-(methylsulfinyl)-butane], an aliphatic isothiocyanate (ITC) naturally derived from cruciferous vegetables and largely known for its chemopreventive potential also appears to possess anti-inflammatory potential. In this study, structural analogs of SF {compound 1 [1-isothiocyanato-4-(methylcarbonyl)-butane] and 2 [1-isothiocyanato-3-(methylcarbonyl)-propane]} containing a carbonyl group in place of the sulfinyl group in SF, were evaluated for their anti-inflammatory activities. In RAW 264.7 cells, the ITCs at non-toxic concentrations caused an inhibition of NO and prostaglandin E2 (PGE2) release through suppressing expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), as well as a reduction in matrix metalloproteinase-9 (MMP-9) expression, secretion and gelatinolytic activity. Further work performed on human monocytes isolated from blood of healthy donors revealed that the ITCs not only suppressed the expression and release of pro-inflammatory mediators IL-1β, IL-6, TNF-α and MMP-9, but also suppressed their antibody-independent phagocytic and chemotactic migratory abilities. These anti-inflammatory activities were mediated through suppression of the NF-κB and MAPK signaling pathways. In addition, the ITCs were revealed to interact with the cysteines in inhibitor of nuclear factor-κB kinase β subunit (IKKβ), which could contribute at least partly to the suppression of NF-κB signaling. In conclusion, results obtained in this study provide deeper insights into the anti-inflammatory properties of SF and its methylcarbonyl analogs and the underlying mechanisms. These compounds thus serve as promising candidates for clinical applications in controlling inflammatory conditions., (Copyright © 2015 Elsevier B.V. All rights reserved.)
- Published
- 2015
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