Decreased expression of immune activator WARS1 and other pro-inflammatory mediators in type 1-like macrophages as an associated mode of action in response to fucoidan from marine brown algae.

BACKGROUND/AIM: Macrophages are key regulators of innate and adaptive immune responses through antigen presentation and the production of inflammatory mediators and growth factors. Imbalances in the activation and inhibition of pro-inflammatory type 1-like macrophages (M1) and anti-inflammatory type 2-like macrophages (M2) are closely associated with various autoimmune and chronic inflammatory diseases, underscoring the need for targeted therapeutic approaches. Numerous studies have shown that sulfated polysaccharides from marine algae, especially fucoidans from brown algae, exhibit a wide range of anti-inflammatory activities. This study aims to investigate the anti-inflammatory mode of action of algae-derived fucoidans in monocyte-derived macrophages and to identify the key regulatory proteins and inflammatory mediators involved. MATERIALS AND METHODS: We applied data-independent mass spectrometry to comprehensively evaluate protein profiles of monocyte-derived M1/M2-like macrophages under the influence of sulfated polysaccharides from different algae species, namely fucoidans from the brown algae Saccharina latissima, Fucus evanescens, and Laminaria digitata, as well as the sulfated xylogalactan from the red alga Delesseria sanguinea. Furthermore, a series of gradually depolymerized fractions of the fucoidan from Saccharina latissima was investigated to elucidate the impact of molecular weight (MW) on protein expression levels and cytokine secretion patterns using membrane-based cytokine arrays and ELISA measurements. RESULTS: Among the tested sulfated polysaccharides, especially the fucoidan from Saccharina latissima showed anti-inflammatory effects. They significantly reduced expression levels of pro-inflammatory tryptophanyl-tRNA synthetase (WARS1), the cytokines interferon gamma-induced protein 10 (IP-10, syn. CXCL10) and macrophage migration inhibitory factor (MIF), as well as urokinase-type plasminogen activator receptor (uPAR) in pro-inflammatory M1-like macrophages, whereby their effects turned out to be independent of the MW. CONCLUSION: Our study provides novel insights into the anti-inflammatory mode of action of fucoidan from Saccharina latissimima on monocyte-derived macrophages. Further in vitro and in vivo studies are required to better understand the underlying molecular pathways, the associated mechanism and to evaluate potential medical applications.