Immunomodulatory potential of sulfated xylated rhamnoglycan from an edible green seaweed Ulva lactuca: Regulation of cytokine expression in CALU-1 cells and prospects for therapeutic applications

Abstract

Green seaweeds, particularly Ulva lactuca, commonly known as sea-lettuce, from the Ulvaceae class, constitute a significant proportion of the global edible seaweed population and serve as a rich storehouse of pharmacologically active compounds, including polysaccharides. In this study, a sulfated (1 → 4) linked xylated rhamnoglycan, (ULP-2), was extracted from Ulva lactuca. ULP-2 displayed significant immunomodulatory properties by modulating the expression of inflammatory cytokines in lipopolysaccharide (LPS)-induced CALU-1 non-small-cell lung cancer (NSCLC) cells. Treatment with ULP-2 at a concentration of 125 μg/mL resulted in a notable downregulation (63%, p < 0.05) of interferon (IFN)-γ gene expression compared to LPS-treated cells. Furthermore, the overexpression of tumor necrosis factor (TNF)-α and interleukin (IL)-1β was significantly attenuated (p < 0.05) with ULP-2 treatment (125 μg/mL), showing substantial downregulation to 0.82% and 1.81%, respectively, compared to LPS-induced cells (29.28% and 94.89%, respectively). Additionally, a noteworthy 1.3-fold reduction in IL-33 expression was observed following the administration of ULP-2 at 125 μg/mL. An upregulation of IFN-α expression, was evident in LPS-induced CALU-1 cells following treatment with ULP-2 within the concentration range of 31.25–125 μg/mL. The structure-activity study reinforced the significance of the presence of polyanionic sulfate and the (1 → 4) linkage in ULP-2 for binding to their respective receptors, influencing the orientation and spatial arrangement of the molecule, and subsequently triggering intracellular signaling pathways linked to the activation of innate immunity. Consequently, this study highlights ULP-2 as a promising natural compound derived from edible seaweed with potential applications in the treatment of inflammatory disorders and immune enhancement.