Sulforaphane regulates phenotypic and functional switching of both induced and spontaneously differentiating human monocytes

Pal, Sanjima; Konkimalla, V. Badireenath

doi:10.1016/j.intimp.2016.03.008

Cited by 34 publications

(21 citation statements)

References 76 publications

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“…Although the current data clearly shows a reduction of leukocyte and platelet recruitment as well ameliorated intestinal neutrophil burden, other cell types (such as monocytes or T cells) are also critically linked to IRI [2]. While the current study focuses on neutrophils, well-described effects of SFN on other cell lines of the innate [20,42] and adaptive [43] immune system suggests that the reduced intestinal inflammatory phenotype following SFN treatment might at least be in part elicited by reduced monocyte or T cell recruitment. Further studies are needed to more precisely dissect these mechanisms.…”

Section: Discussionmentioning

confidence: 70%

Sulforaphane Elicits Protective Effects in Intestinal Ischemia Reperfusion Injury

Chen

Mohr

Heitplatz

et al. 2020

IJMS

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Intestinal ischemia reperfusion injury (IRI) is an inherent, unavoidable event of intestinal transplantation, contributing to allograft failure and rejection. The inflammatory state elicited by intestinal IRI is characterized by heightened leukocyte recruitment to the gut, which is amplified by a cross-talk with platelets at the endothelial border. Sulforaphane (SFN), a naturally occurring isothiocyanate, exhibits anti-inflammatory characteristics and has been shown to reduce platelet activation and block leukocyte adhesion. Thus, the aim of this study was to investigate protective effects and mechanism of action of SFN in a murine model of intestinal IRI. Intestinal IRI was induced by superior mesenteric artery occlusion for 30 min, followed by reperfusion for 2 h, 8 h or 24 h. To investigate cellular interactions, leukocytes were in vivo stained with rhodamine and platelets were harvested from donor animals and ex vivo stained. Mice (C57BL/6J) were divided into three groups: (1) control, (2) SFN treatment 24 h prior to reperfusion and (3) SFN treatment 24 h prior to platelet donation. Leukocyte and platelet recruitment was analyzed via intravital microscopy. Tissue was analyzed for morphological alterations in intestinal mucosa, barrier permeability, and leukocyte infiltration. Leukocyte rolling and adhesion was significantly reduced 2 h and 8 h after reperfusion. Mice receiving SFN treated platelets exhibited significantly decreased leukocyte and platelet recruitment. SFN showed protection for intestinal tissue with less damage observed in histopathological and ultrastructural evaluation. In summary, the data presented provide evidence for SFN as a potential therapeutic strategy against intestinal IRI.

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Section: Discussionmentioning

confidence: 70%

Sulforaphane Elicits Protective Effects in Intestinal Ischemia Reperfusion Injury

Chen

Mohr

Heitplatz

et al. 2020

IJMS

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“…Kumar et al demonstrated that in vitro the development of human myeloid-derived suppressor cells (MDSCs) from CD14+ monocytes cultured in glioma conditioned medium was inhibited by SFN, which may enhance T-cell proliferation ( 6 ). On the other hand, the study by Pal et al suggested that effects induced by SFN eventually shifted human monocyte polarization to a direction specific to M2 macrophages, promoting an anti-inflammatory phenotype ( 7 ). Geisel et al reported that in a murine system, SFN led to diminished IL-12 and IL-23 expression by dendritic cells (DCs) eventually interfering with pro-inflammatory immune responses ( 8 ).…”

Section: Introductionmentioning

confidence: 99%

Sulforaphane Inhibits Inflammatory Responses of Primary Human T-Cells by Increasing ROS and Depleting Glutathione

et al. 2018

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The activity and function of T-cells are influenced by the intra- and extracellular redox milieu. Oxidative stress induces hypo responsiveness of untransformed T-cells. Vice versa increased glutathione (GSH) levels or decreased levels of reactive oxygen species (ROS) prime T-cell metabolism for inflammation, e.g., in rheumatoid arthritis. Therefore, balancing the T-cell redox milieu may represent a promising new option for therapeutic immune modulation. Here we show that sulforaphane (SFN), a compound derived from plants of the Brassicaceae family, e.g., broccoli, induces a pro-oxidative state in untransformed human T-cells of healthy donors or RA patients. This manifested as an increase of intracellular ROS and a marked decrease of GSH. Consistently, increased global cysteine sulfenylation was detected. Importantly, a major target for SFN-mediated protein oxidation was STAT3, a transcription factor involved in the regulation of TH17-related genes. Accordingly, SFN significantly inhibited the activation of untransformed human T-cells derived from healthy donors or RA patients, and downregulated the expression of the transcription factor RORγt, and the TH17-related cytokines IL-17A, IL-17F, and IL-22, which play a major role within the pathophysiology of many chronic inflammatory/autoimmune diseases. The inhibitory effects of SFN could be abolished by exogenously supplied GSH and by the GSH replenishing antioxidant N-acetylcysteine (NAC). Together, our study provides mechanistic insights into the mode of action of the natural substance SFN. It specifically exerts TH17 prone immunosuppressive effects on untransformed human T-cells by decreasing GSH and accumulation of ROS. Thus, SFN may offer novel clinical options for the treatment of TH17 related chronic inflammatory/autoimmune diseases such as rheumatoid arthritis.

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“…Sulforaphane also exerts an anti-angiogenic effect by inhibiting angiogenesis-activating transcription factors, such as HIF-1-alpha and c-Myc, and by reducing the production of matrix metallo-proteinase-2 and endothelial cell proliferation [ 13 ]. Several studies have highlighted the anti-inflammatory potential of sulforaphane, which is able to reduce inducible nitric oxide synthase and cyclooxygenase-2 expression as well as the secretion of tumor necrosis factor-alpha in cultivated macrophages [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Antiproliferative, Proapoptotic, Antioxidant and Antimicrobial Effects of Sinapis nigra L. and Sinapis alba L. Extracts

et al. 2018

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High Brassicaceae consumption reduces the risk of developing several cancer types, probably due to high levels of glucosinolates. Extracts from Sinapis nigra L. (S. nigra) and Sinapis alba L. (S. alba) have been obtained from leaves and seeds under different conditions using ethanol/water mixtures because their glucosinolates are well accepted by the food industry. The EtOH/H2O 8:2 mixture gives better yields in glucosinolate amounts from ground seeds, mainly, sinalbin in S. alba and sinigrin in S. nigra. The highest antiproliferative activity in both non-tumor and tumor cell lines was induced by S. alba seeds extract. To evaluate whether the effect of Sinapis species (spp) was only due to glucosinolate content or whether it was influenced by the extracts’ complexity, cells were treated with extracts or glucosinolates, in the presence of myrosinase. Pure sinigrin did not modify cell proliferation, while pure sinalbin was less effective than the extract. The addition of myrosinase increased the antiproliferative effects of the S. nigra extract and sinigrin. Antiproliferative activity was correlated to Mitogen-Activated Protein Kinases modulation, which was cell and extract-dependent. Cell-cycle analysis evidenced a proapoptotic effect of S. alba on both tumor cell lines and of S. nigra only on HCT 116. Both extracts showed good antimicrobial activity in disc diffusion tests and on ready-to-eat fresh salad. These results underline the potential effects of Sinapis spp in chemoprevention and food preservation.

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Sulforaphane regulates phenotypic and functional switching of both induced and spontaneously differentiating human monocytes

Cited by 34 publications

References 76 publications

Sulforaphane Elicits Protective Effects in Intestinal Ischemia Reperfusion Injury

Sulforaphane Elicits Protective Effects in Intestinal Ischemia Reperfusion Injury

Sulforaphane Inhibits Inflammatory Responses of Primary Human T-Cells by Increasing ROS and Depleting Glutathione

Antiproliferative, Proapoptotic, Antioxidant and Antimicrobial Effects of Sinapis nigra L. and Sinapis alba L. Extracts

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