Suppression of LPS‐induced transcription and cytokine secretion by the dietary isothiocyanate sulforaphane

Abstract

Scope: Diets rich in cruciferous vegetables are associated with lower levels of pro-inflammatory cytokines, which may contribute to potential health-promoting properties of these vegetables. We investigate whether sulforaphane (SF), an isothiocyanate (ITC) obtained from broccoli, could suppress LPS-induced transcription and subsequent pro-inflammatory cytokine secretion at a physiologically relevant concentration using in vitro models of chronic inflammation. Methods and results:We find that exposure of the LPS receptor Toll-like receptor-4 (TLR4) to physiologically appropriate concentrations of SF under non-reducing conditions results in covalent modification of cysteine residues 246 and 609. We further demonstrate that the changes in expression of 1210 genes (p ࣘ 0.01) in THP-1 monocytes and the secretion of pro-inflammatory cytokines in both human peripheral blood mononuclear cells (PBMCs) and THP-1 monocytes induced by LPS exposure can be completely suppressed through exposure with physiologically appropriate concentrations of SF. Finally, we show that in vivo exposure of human PBMCs to ITCs within human circulation reduces secretion of pro-inflammatory cytokines following subsequent ex vivo LPS challenge (p < 0.001). Conclusion: Covalent modification of TLR4 by ITCs and resultant suppression of LPS-induced cell signalling could lead to reductions in levels of pro-inflammatory cytokines in people with chronic diseases who consume diets rich in cruciferous vegetables.

Sulforaphane suppresses cell growth and collagen expression of keloid fibroblasts

“…A previous report showed that sulforaphane inhibited the secretion of IL‐6 from PBMC . In this study, sulforaphane also inhibited IL‐6 secretion from PBMC especially under stimulation by LPS (Figure A).…”

“…A previous report showed that sulforaphane inhibited the secretion of IL-6 from PBMC. 24 In this study, sulforaphane also inhibited IL-6 secretion from PBMC especially under stimulation by LPS ( Figure 6A). IL-6 mRNA expression in KF112 cells and the concentration of IL-6 protein in the supernatant were increased by the coculture with PBMC at 24 and 96 hours ( Figure 6B and C).…”

“…Sulforaphane was reported to show anti-cancer activities, as well as anti-inflammatory and anti-fibrotic effects. As one of the mechanisms, IL-6 suppression by sulforaphane was shown in PBMC 24 and other cells. 18,19 Moreover, STAT3 inhibition by sulforaphane was shown in prostate cancer cells.…”

Thiram modulates pro-inflammatory mediators in RAW 264.7 murine macrophage cells

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The potential role of some phytochemicals in recognition of mitochondrial damage-associated molecular patterns

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