Examination of Novel Immunomodulatory Effects of L-Sulforaphane

Abstract

The dietary isothiocyanate L-sulforaphane (LSF), derived from cruciferous vegetables, is reported to have several beneficial biological properties, including anti-inflammatory and immunomodulatory effects. However, there is limited data on how LSF modulates these effects in human immune cells. The present study was designed to investigate the immunomodulatory effects of LSF (10 µM and 50 µM) on peripheral blood mononuclear cell (PBMC) populations and cytokine secretion in healthy adult volunteers (n = 14), in the presence or absence of bacterial (lipopolysaccharide) and viral (imiquimod) toll-like receptor (TLRs) stimulations. Here, we found that LSF reduced pro-inflammatory cytokines interleukin (IL)-6, IL-1b, and chemokines monocyte chemoattractant protein (MCP)-1 irrespective of TLR stimulations. This result was associated with LSF significantly reducing the proportion of natural killer (NK) cells and monocytes while increasing the proportions of dendritic cells (DCs), T cells and B cells. We found a novel effect of LSF in relation to reducing cluster of differentiation (CD) 14+ monocytes while simultaneously increasing monocyte-derived DCs (moDCs: lineage-Human Leukocyte Antigen-DR isotype (HLA-DR)+CD11blow-high CD11chigh). LSF was also shown to induce a 3.9-fold increase in the antioxidant response element (ARE) activity in a human monocyte cell line (THP-1). Our results provide important insights into the immunomodulatory effects of LSF, showing in human PBMCs an ability to drive differentiation of monocytes towards an immature monocyte-derived dendritic cell phenotype with potentially important biological functions. These findings provide insights into the potential role of LSF as a novel immunomodulatory drug candidate and supports the need for further preclinical and phase I clinical studies.

Sulforaphane, an Nrf-2 Agonist, Modulates Oxidative Stress and Inflammation in a Rat Model of Cuprizone-Induced Cardiotoxicity and Hepatotoxicity

“…SF demonstrated anti-inflammatory and anti-oxidative activities as demonstrated previously [ 87 – 89 ]. SF was capable of reducing both IL-1β and IFN-γ levels, this run in agreement with several studies [ 90 – 93 ], signifying the role of SF as an antioxidant bioactive molecule with anti-inflammatory potential.…”

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

“…These findings were consistent in all four samples. Genes encoding for the expression of cytokines and chemokines such as IL-6, IL-1A, IL-1B, EB13, CXCL5, and CXCL1, were primarily downregulated, highlighting the anti-inflammatory signature of LSF 23,36,38 .…”

“…A limitation of our study is that the potential effects of key SFN metabolites were not explicitly investigated. We have recently shown that although not as potent as LSF, metabolites such as SFN-Cys and SFN-NAC, have important roles in anti-inflammatory pathways 23 . Here, we show acetylation of -tubulin following in vivo administration of LSF (Fig 6).…”

“…Under basal conditions, Nrf2 is sequestered in the cytosol by Kelch-like ECH-associated protein 1 (Keap1) 22 . Recently it has been shown that LSF causes a reduction of pro-inflammatory cytokine and chemokine production, and alleviates inflammation by targeting antigen-presenting cells 23 .…”

Sulforaphane Impact on Reactive Oxygen Species (ROS) in Bladder Carcinoma

“…Meanwhile, the therapeutic options for bladder cancer have been considerably widened by the introduction of immune checkpoint inhibitors targeting cytotoxic T lymphocyte antigen 4 (CTLA4) and programmed death (ligand) 1 (PD-1/PDL1). In view of these new treatment modalities aimed at suppressing tumor cell inhibition of anticancer immune responses [ 117 ], it has become evident that SFN may exert immunomodulatory effects by altering the proportion of natural killer cells, monocytes, dendritic cells, T- and B-cells [ 118 ]. Investigation of human peripheral blood T-cells derived from healthy donors showed that SFN induces a significant accumulation of ROS in the T-cells, which resulted in the inhibition of T-cell activation and T-cell effector functions [ 119 ].…”