FTY720 restores endothelial cell permeability induced by malaria sera

Oggungwan, Karanyaporn; Glaharn, Supattra; Ampawong, Sumate; Krudsood, Srivicha; Viriyavejakul, Parnpen

doi:10.1038/s41598-018-28536-1

Cited by 13 publications

(11 citation statements)

References 34 publications

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“…MUG-Chor1 and U-CH1 are two of the most popular sacrum chordoma cell lines and, as such, were chosen for our experiments. We treated the two sacrum chordoma cell lines with different concentrations of FTY20, and respectively terminated the culture at 24, 48, 72, 96 and 120 h. MTS assays showed that FTY720 significantly suppressed the growth of sacrum chordoma cells in both a dose-and time-dependent manner [31,32]. The colony formation and EdU assay results also suggested that FTY720 significantly inhibited the growth of sacrum chordoma cells.…”

Section: Discussionmentioning

confidence: 99%

Fingolimod inhibits proliferation and epithelial–mesenchymal transition in sacral chordoma by inactivating IL-6/STAT3 signalling

Wang

et al. 2020

Bioscience Reports

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Purpose: To explore the sensitivity of the immunosuppressive agent fingolimod (FTY720) in chordoma and determine whether it can serve as an appropriate alternate treatment for unresectable tumours in patients after incomplete surgery. Methods: Cell viability assays, colony formation assays and EdU assays were performed to evaluate the sensitivity of chordoma cell lines to FTY720. Transwell invasion assays, wound healing assays, flow cytometry, cell cycle analysis, immunofluorescence analysis, Western blotting analysis and enzyme-linked immunosorbent assays (ELISAs) were performed to evaluate cell invasion, epithelial–mesenchymal transition (EMT) and activation of related pathways after treatment with FTY720. The effect of FTY720 was also evaluated in vivo in a xenograft model. Results: We found that FTY720 inhibited the proliferation, invasion and metastasis of sacral chordoma cells (P < 0.01). FTY720 also inhibited the proliferation of tumour cells in a xenograft model using sacral chordoma cell lines (P < 0.01). The mechanism was related to the EMT and apoptosis of chordoma cells and inactivation of IL-6/STAT3 signalling in vitro and in vivo. Conclusions: Our findings indicate that FTY720 may be an effective therapeutic agent against chordoma. These findings suggest that FTY720 is a novel agent that can treat locally advanced and metastatic chordoma.

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Section: Discussionmentioning

confidence: 99%

Fingolimod inhibits proliferation and epithelial–mesenchymal transition in sacral chordoma by inactivating IL-6/STAT3 signalling

Wang

et al. 2020

Bioscience Reports

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“…Interestingly, inverse association of S1P with endothelial glycocalyx breakdown products have been demonstrated in Indonesian adults patients with falciparum infection (Yeo et al, 2019). Further, increased permeability of endothelial cells induced by sera from individuals with complicated falciparum malaria has been found to reverse with phosphorylated FTY720, an S1P agonist (Oggungwan et al, 2018). This indicates that S1P bioavailability could be instrumental in attenuating endothelial damage and ensuing protection from severe malaria.…”

Section: S1p and Its Association With Malariamentioning

confidence: 97%

“…Significantly high permeability was recorded after incubation with serum from complicated patients with falciparum malaria compared to uncomplicated falciparum patients and vivax infected patients. Treatment with FTY720 before and after incubation of sera significantly reduced and prevented sera induced increase in endothelial cell permeability (Oggungwan et al, 2018) 5 CBA/CaJ mice Mice were infected with PbA for induction of ECM and with Plasmodium yoelii for malarial hyperparasitemia without neurological impairment. Treatment with FTY720 was investigated to understand the pathogenesis Recruitment of activated leukocytes (CD8+ T cells and ICAM+ macrophages), and neutrophils to post-capillary venules prevents venous blood efflux from the brains severely, which leads to vasogenic edema in ECM.…”

Section: Human Erythrocytesmentioning

confidence: 99%

Sphingosine 1-Phosphate in Malaria Pathogenesis and Its Implication in Therapeutic Opportunities

Dhangadamajhi

Singh

2020

Front. Cell. Infect. Microbiol.

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Sphingosine 1-Phosphate (S1P) is a bioactive lipid intermediate in the sphingolipid metabolism, which exist in two pools, intracellular and extracellular, and each pool has a different function. The circulating extracellular pool, specifically the plasma S1P is shown to be important in regulating various physiological processes related to malaria pathogenesis in recent years. Although blood cells (red blood cells and platelets), vascular endothelial cells and hepatocytes are considered as the important sources of plasma S1P, their extent of contribution is still debated. The red blood cells (RBCs) and platelets serve as a major repository of intracellular S1P due to lack, or low activity of S1P degrading enzymes, however, contribution of platelets toward maintaining plasma S1P is shown negligible under normal condition. Substantial evidences suggest platelets loss during falciparum infection as a contributing factor for severe malaria. However, platelets function as a source for plasma S1P in malaria needs to be examined experimentally. RBC being the preferential site for parasite seclusion, and having the ability of trans-cellular S1P transportation to EC upon tight cell-cell contact, might play critical role in differential S1P distribution and parasite growth. In the present review, we have summarized the significance of both the S1P pools in the context of malaria, and how the RBC content of S1P can be channelized in better ways for its possible implication in therapeutic opportunities to control malaria.

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“…Furthermore, the SL metabolite is suspected to be involved in the onset and progression of psychiatric disorders and pain syndrome (75) which might provide evidence to find a missing link between GI infl ammation and psychosomatic manifestations. The S1P analogue FTY720 (Fingolimod) was originally used in treatment of multiple sclerosis by modulating immune cell chemotaxis, but has been also suggested for cancer treatment (142) and for restoring endothelial barrier dysfunction (143).…”

Section: Sls and The Drug Industrymentioning

confidence: 99%

The Impact of Dietary Sphingolipids on Intestinal Microbiota and Gastrointestinal Immune Homeostasis

et al. 2021

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The large surfaces of gastrointestinal (GI) organs are well adapted to their diverse tasks of selective nutritional uptake and defense against the external environment. To maintain a functional balance, a vast number of immune cells is located within the mucosa. A strictly regulated immune response is required to impede constant inflammation and to maintain barrier function. An increasing prevalence of GI diseases has been reported in Western societies over the past decades. This surge in GI disorders has been linked to dietary changes followed by an imbalance of the gut microbiome, leading to a chronic, low grade inflammation of the gut epithelium. To counteract the increasing health care costs associated with diseases, it is paramount to understand the mechanisms driving immuno-nutrition, the associations between nutritional compounds, the commensal gut microbiota, and the host immune response. Dietary compounds such as lipids, play a central role in GI barrier function. Bioactive sphingolipids (SLs), e.g. sphingomyelin (SM), sphingosine (Sph), ceramide (Cer), sphingosine-1- phosphate (S1P) and ceramide-1-phosphate (C1P) may derive from dietary SLs ingested through the diet. They are not only integral components of cell membranes, they additionally modulate cell trafficking and are precursors for mediators and second messenger molecules. By regulating intracellular calcium levels, cell motility, cell proliferation and apoptosis, SL metabolites have been described to influence GI immune homeostasis positively and detrimentally. Furthermore, dietary SLs are suggested to induce a shift in the gut microbiota. Modes of action range from competing with the commensal bacteria for intestinal cell attachment to prevention from pathogen invasion by regulating innate and immediate defense mechanisms. SL metabolites can also be produced by gut microorganisms, directly impacting host metabolic pathways. This review aims to summarize recent findings on SL signaling and functional variations of dietary SLs. We highlight novel insights in SL homeostasis and SL impact on GI barrier function, which is directly linked to changes of the intestinal microbiota. Knowledge gaps in current literature will be discussed to address questions relevant for understanding the pivotal role of dietary SLs on chronic, low grade inflammation and to define a balanced and healthy diet for disease prevention and treatment.

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FTY720 restores endothelial cell permeability induced by malaria sera

Cited by 13 publications

References 34 publications

Fingolimod inhibits proliferation and epithelial–mesenchymal transition in sacral chordoma by inactivating IL-6/STAT3 signalling

Fingolimod inhibits proliferation and epithelial–mesenchymal transition in sacral chordoma by inactivating IL-6/STAT3 signalling

Sphingosine 1-Phosphate in Malaria Pathogenesis and Its Implication in Therapeutic Opportunities

The Impact of Dietary Sphingolipids on Intestinal Microbiota and Gastrointestinal Immune Homeostasis

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