Antithetical effects of hemicellulase-treated Agaricus blazei on the maturation of murine bone-marrow-derived dendritic cells

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Abstract
We report the effects of hemicellulase‐treated Agaricus blazei (ABH) on the maturation of bone‐marrow‐derived dendritic cells (BMDCs). ABH activated immature BMDCs, inducing up‐regulation of surface molecules, such as CD40, CD80 and major histocompatibility complex class I antigens, as well as inducing allogeneic T‐cell proliferation and T helper type 1 cell development. However, unlike lipopolysaccharide (LPS), ABH did not stimulate the BMDCs to produce proinflammatory cytokines, such as interleukin‐12 (IL‐12) p40, tumour necrosis factor‐α, or IL‐1β. In addition, ABH suppressed LPS‐induced DC responses. Pretreatment of DCs with ABH markedly reduced the levels of LPS‐induced cytokine secretion, while only slightly decreasing up‐regulation of the surface molecules involved in maturation. ABH also had a significant impact on peptidoglycan‐induced or CpG oligodeoxynucleotide‐induced IL‐12p40 production in DCs. The inhibition of LPS‐induced responses was not associated with a cytotoxic effect of ABH nor with an anti‐inflammatory effect of IL‐10. However, ABH decreased NF‐κB‐induced reporter gene expression in LPS‐stimulated J774.1 cells. Interestingly, DCs preincubated with ABH and then stimulated with LPS augmented T helper type 1 responses in culture with allogeneic T cells as compared to LPS‐stimulated but non‐ABH‐pretreated DCs. These observations suggest that ABH regulates DC‐mediated responses.