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- W2999776369 abstract "Rheumatoid arthritis is driven by an array of cytokines that include TNF-α synthesised by T-cells and macrophages. Sulphated disaccharides are released by heparanase during inflammation to inhibit T-cell function. These compounds, including the synthetic analogue sucrose octasulphate (SOS) were shown to inhibit experimental arthritis in rodents and reduce T-cell function. We have shown that SOS inhibits monocyte-to-macrophage differentiation. The current study was conducted to explore whether SOS can modulate macrophage polarisation into a pro-inflammatory (M1) or anti-inflammatory (M2) phenotype.U937 human monocytes were pre-treated with SOS (10⁻¹¹ to 10⁻⁴ M) for 2h prior to the induction of differentiation with 8nM phorbol 12-myristate 13-acetate (PMA) for 48h. Cell differentiation was determined by cell count, cell proliferation assay and flow cytometry. The cells were then washed and re-suspended in fresh medium for 24h followed by 1μg/ml LPS or 10ng/ml IL-4 stimulation for 6h to induce TNF-α/IL-10 synthesis (evaluated by ELISA) and to polarise the cells into an M1 or M2 phenotype respectively (assessed by flow cytometry and RT-PCR).SOS inhibited PMA-induced monocytes differentiation by down-regulating cell adhesion (CD11a, CD11b), M1 phenotype (CD14, CD68, CD86) surface markers and CD14 mRNA expression. SOS up-regulated M2 phenotype (CD206, CD163) surface markers and CD200R mRNA expression. We also found down-regulation of LPS-induced TNF-α synthesis and up-regulated IL-4 induced IL-10 synthesis.Our results indicate that SOS treatment inhibits the differentiation of monocytes into M1 phenotype, and polarise into the M2 phenotype in a concentration-dependent manner, suggesting that SOS contributes to anti-inflammatory responses." @default.
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- W2999776369 date "2019-01-01" @default.
- W2999776369 modified "2023-09-26" @default.
- W2999776369 title "Sucrose octasulphate regulates the expression of M1 and M2 macrophage-specific markers in U937 monocytes" @default.
- W2999776369 hasPublicationYear "2019" @default.
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