Kawamura Masaki, Kasai Hirotake, He Limin, Deng Xuewen, Yamashita Atsuya, Terunuma Hiroshi, Horiuchi Isao, Tanabe Fuminori, Ito Masahiko
Department of Alternative Medicine and Bioregulation, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan.
Immunology. 2005 Mar;114(3):397-409. doi: 10.1111/j.1365-2567.2004.02106.x.
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-alpha, or IL-1beta. 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-kappaB-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.
我们报告了经半纤维素酶处理的姬松茸（ABH）对骨髓来源树突状细胞（BMDC）成熟的影响。ABH激活未成熟的BMDC，诱导表面分子如CD40、CD80和主要组织相容性复合体I类抗原的上调，同时诱导同种异体T细胞增殖和1型辅助性T细胞发育。然而，与脂多糖（LPS）不同，ABH不会刺激BMDC产生促炎细胞因子，如白细胞介素-12（IL-12）p40、肿瘤坏死因子-α或IL-1β。此外，ABH抑制LPS诱导的树突状细胞反应。用ABH预处理树突状细胞可显著降低LPS诱导的细胞因子分泌水平，而仅略微降低参与成熟的表面分子的上调。ABH对肽聚糖诱导或CpG寡脱氧核苷酸诱导的树突状细胞中IL-12p40的产生也有显著影响。对LPS诱导反应的抑制与ABH的细胞毒性作用或IL-10的抗炎作用无关。然而，ABH降低了LPS刺激的J774.1细胞中NF-κB诱导的报告基因表达。有趣的是，与LPS刺激但未用ABH预处理的树突状细胞相比，用ABH预孵育然后用LPS刺激的树突状细胞在与同种异体T细胞共培养时增强了1型辅助性T细胞反应。这些观察结果表明ABH调节树突状细胞介导的反应。
