Sucrose octasulphate regulates the expression of M1 and M2 macrophage-specific markers in U937 monocytes

Conference poster


Bajwa, P., Garrido Mesa, N., Seed, M. and Ayoub, S. 2019. Sucrose octasulphate regulates the expression of M1 and M2 macrophage-specific markers in U937 monocytes. 14th World Congress on Inflammation 2019. Sydney, AU 15 - 19 Sep 2019 World Congress on Inflammation.
AuthorsBajwa, P., Garrido Mesa, N., Seed, M. and Ayoub, S.
TypeConference poster
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.

Year2019
Conference14th World Congress on Inflammation 2019
PublisherWorld Congress on Inflammation
Publication dates
PrintSep 2019
Publication process dates
Completed16 Sep 2019
Deposited16 Jan 2020
Book title14th World Congress on Inflammation 2019: Abstract Book
Web address (URL)https://wci2019.org/download/WCI%202019%20Abstract%20Book.pdf
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