Mazarakis Nadia, Anderson Jeremy, Toh Zheng Quan, Higgins Rachel A, Do Lien Anh Ha, Luwor Rodney B, Snibson Kenneth J, Karagiannis Tom C, Licciardi Paul V
Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Parkville, VIC 3010, Australia.
New Vaccines, Infection and Immunity, Murdoch Children's Research Institute, Melbourne, VIC 3052, Australia.
Nutrients. 2021 Feb 12;13(2):602. doi: 10.3390/nu13020602.
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 ( = 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-1β, 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)CD11b CD11c). 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.
源自十字花科蔬菜的膳食异硫氰酸酯L-萝卜硫素(LSF)据报道具有多种有益的生物学特性,包括抗炎和免疫调节作用。然而,关于LSF如何调节人类免疫细胞中的这些作用的数据有限。本研究旨在调查LSF(10 μM和50 μM)在有或无细菌(脂多糖)和病毒(咪喹莫特)Toll样受体(TLR)刺激的情况下,对健康成年志愿者(n = 14)外周血单个核细胞(PBMC)群体和细胞因子分泌的免疫调节作用。在此,我们发现无论TLR刺激如何,LSF均可降低促炎细胞因子白细胞介素(IL)-6、IL-1β以及趋化因子单核细胞趋化蛋白(MCP)-1。这一结果与LSF显著降低自然杀伤(NK)细胞和单核细胞的比例,同时增加树突状细胞(DC)、T细胞和B细胞的比例有关。我们发现LSF具有一种新的作用,即降低分化簇(CD)14单核细胞的比例,同时增加单核细胞衍生的DC(moDC:谱系 - 人类白细胞抗原 - DR同种型(HLA-DR)CD11b CD11c)。在人单核细胞系(THP-1)中,LSF还被证明可使抗氧化反应元件(ARE)活性增加3.9倍。我们的结果为LSF的免疫调节作用提供了重要见解,表明在人类PBMC中,LSF有能力驱动单核细胞向具有潜在重要生物学功能的未成熟单核细胞衍生树突状细胞表型分化。这些发现为LSF作为新型免疫调节药物候选物的潜在作用提供了见解,并支持进一步进行临床前和I期临床研究的必要性。