Immunomodulatory Activity of a Novel, Synthetic Beta-glucan (beta-glu6) in Murine Macrophages and Human Peripheral Blood Mononuclear Cells

Natural beta-glucans extracted from plants and fungi have been used in clinical therapies since the late 20th century. However, the heterogeneity of natural beta-glucans limits their clinical applicability. We have synthesized beta-glu6, which is an analog of the lentinan basic unit, beta-(1 -> 6)-branched beta-(1 -> 3) glucohexaose, that contains an alpha-(1 -> 3)-linked bond. We have demonstrated the stimulatory effect of this molecule on the immune response, but the mechanisms by which beta-glu6 activates innate immunity have not been elucidated. In this study, murine macrophages and human PBMCs were used to evaluate the immunomodulatory effects of beta-glu6. We showed that beta-glu6 activated ERK and c-Raf phosphorylation but suppressed the AKT signaling pathway in murine macrophages. Additionally, beta-glu6 enhanced the secretion of large levels of cytokines and chemokines, including CD54, IL-1 alpha, IL-1 beta, IL-16, IL-17, IL-23, IFN-gamma, CCL1, CCL3, CCL4, CCL12, CXCL10, tissue inhibitor of metalloproteinase-1 (TIMP-1) and G-CSF in murine macrophages as well as IL-6, CCL2, CCL3, CCL5, CXCL1 and macrophage migration inhibitory factor (MIF) in human PBMCs. In summary, it demonstrates the immunomodulatory activity of beta-glu6 in innate immunity.