Immunomodulatory activity of a novel, synthetic beta-glucan (?-glu6) in murine macrophages and human peripheral blood mononuclear cells.

ABSTRACT: Natural ?-glucans extracted from plants and fungi have been used in clinical therapies since the late 20th century. However, the heterogeneity of natural ?-glucans limits their clinical applicability. We have synthesized ?-glu6, which is an analog of the lentinan basic unit, ?-(1?6)-branched ?-(1?3) glucohexaose, that contains an ?-(1?3)-linked bond. We have demonstrated the stimulatory effect of this molecule on the immune response, but the mechanisms by which ?-glu6 activates innate immunity have not been elucidated. In this study, murine macrophages and human PBMCs were used to evaluate the immunomodulatory effects of ?-glu6. We showed that ?-glu6 activated ERK and c-Raf phosphorylation but suppressed the AKT signaling pathway in murine macrophages. Additionally, ?-glu6 enhanced the secretion of large levels of cytokines and chemokines, including CD54, IL-1?, IL-1?, IL-16, IL-17, IL-23, IFN-?, 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 ?-glu6 in innate immunity.

SUBMITTER: Li X 

PROVIDER: S-EPMC3819285 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature