Mechanism of enhanced hematopoietic response by soluble beta-glucan SCG in cyclophosphamide-treated mice.
SCG is a major 6-branched 1,3-beta-D-glucan in Sparassis crispa Fr. SCG shows antitumor activity and also enhances the hematopoietic response in cyclophosphamide (CY)-treated mice. In the present study, the molecular mechanism of the enhancement of the hematopoietic response was investigated. The levels of interferon-(IFN-)gamma, tumor necrosis factor-(TNF-)alpha, granulocyte-macrophage-colony stimulating factor (GM-CSF), interleukin-(IL-) 6 and IL-12p70 were significantly increased by SCG in CY-treated mice. GM-CSF production in the splenocytes from the CY-treated mice was higher than that in normal mice regardless of SCG stimulation. Neutralizing GM-CSF significantly inhibited the induction of IFN-gamma, TNF-alpha and IL-12p70 by SCG. The level of cytokine induction by SCG was regulated by the amount of endogenous GM-CSF produced in response to CY treatment in a dose-dependent manner. The expression of beta-glucan receptors, such as CR3 and dectin-1, was up-regulated by CY treatment. Blocking dectin-1 significantly inhibited the induction of TNF-alpha and IL-12p70 production by SCG. Taken together, these results suggest that the key factors in the cytokine induction in CY-treated mice were the enhanced levels of both endogenous GM-CSF production and dectin-1 expression.
Harada
Toshie
T
Laboratory for Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy & Life Science, Japan.
Kawaminami
Hiromi
H
Miura
Noriko N
NN
Adachi
Yoshiyuki
Y
Nakajima
Mitsuhiro
M
Yadomae
Toshiro
T
Ohno
Naohito
N
D000818:Animals; D001487:Basidiomycota / Q000737:chemistry; D003520:Cyclophosphamide / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis* / Q000097:blood / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006410:Hematopoiesis / Q000187:drug effects*; D007155:Immunologic Factors / Q000494:pharmacology*; D037181:Lectins, C-Type; D007958:Leukocyte Count; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D013154:Spleen / Q000166:cytology; D047071:beta-Glucans / Q000494:pharmacology*; D000099181:Dectin-1
D003520:Cyclophosphamide; D016207:Cytokines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007155:Immunologic Factors; D037181:Lectins, C-Type; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011971:Receptors, Immunologic; D047071:beta-Glucans; D000099181:Dectin-1; C045268:beta-glucan receptor