IL‐12 Production Induced by Agaricus blazei Fraction H (ABH) Involves Toll‐like Receptor (TLR)

Abstract
Agaricus blazei Murill is an edible fungus used in traditional medicine, which has various well‐documented medicinal properties. In the present study, we investigated the effects of hemicellulase‐derived mycelia extract (Agaricus blazei fraction H: ABH) on the immune system. First, we examined the cytokine‐inducing activity of ABH on human peripheral mononuclear cells (PBMC). The results indicated that ABH induced expression of IL‐12, a cytokine known to be a critical regulator of cellular immune responses. Flow cytometric analysis demonstrated the induction of IL‐12 production by the CD14‐positive cell population, consisting of monocytes/macrophages (Mo/Mφ). Furthermore, the elimination of Mo/Mφ attenuated IL‐12 production in PBMC. ABH‐induced IL‐12 production was inhibited by anti‐CD14 and anti‐TLR4 antibodies but not by anti‐TLR2 antibody. The activity of ABH was not inhibited by polymyxin B, while the activity of lipopolysaccharide used as a reference was inhibited. Oral administration of ABH enhanced natural killer (NK) activity in the spleen. These findings suggest that ABH activated Mo/Mφ in a manner dependent on CD14/TLR4 and NK activity.

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