Immunomodulatory activity of a novel, synthetic beta-glucan (β-glu6) in murine macrophages and human peripheral blood mononuclear cells.
Natural β-glucans extracted from plants and fungi have been used in clinical therapies since the late 20th century. However, the heterogeneity of natural β-glucans limits their clinical applicability. We have synthesized β-glu6, which is an analog of the lentinan basic unit, β-(1→6)-branched β-(1→3) glucohexaose, that contains an α-(1→3)-linked bond. We have demonstrated the stimulatory effect of this molecule on the immune response, but the mechanisms by which β-glu6 activates innate immunity have not been elucidated. In this study, murine macrophages and human PBMCs were used to evaluate the immunomodulatory effects of β-glu6. We showed that β-glu6 activated ERK and c-Raf phosphorylation but suppressed the AKT signaling pathway in murine macrophages. Additionally, β-glu6 enhanced the secretion of large levels of cytokines and chemokines, including CD54, IL-1α, IL-1β, IL-16, IL-17, IL-23, IFN-γ, 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 β-glu6 in innate immunity.
Key Laboratory of Medical Molecular Virology of MOE and MOH, Institute of Medical Microbiology and Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.
Xiaofei
X
Li
Jing
J
Wang
Wei
W
Wang
Chunhong
C
Liu
Shuhui
S
Sun
Jianxin
J
Gu
Xun
X
Wang
Diana
D
Boraschi
Yuxian
Y
Huang
Di
D
Qu
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D007155:Immunologic Factors / Q000737:chemistry* / Q000494:pharmacology*; D007371:Interferon-gamma / Q000378:metabolism; D019410:Interleukin-16 / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D053759:Interleukin-23 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D047071:beta-Glucans / Q000737:chemistry* / Q000494:pharmacology*
D016207:Cytokines; D007155:Immunologic Factors; D019410:Interleukin-16; D020381:Interleukin-17; D053583:Interleukin-1beta; D053759:Interleukin-23; D015850:Interleukin-6; D019715:Tissue Inhibitor of Metalloproteinase-1; D047071:beta-Glucans; D016179:Granulocyte Colony-Stimulating Factor; D007371:Interferon-gamma