Davis Renee, Taylor Alex, Nally Regan, Benson Kathleen F, Stamets Paul, Jensen Gitte S
Fungi Perfecti, Olympia, WA 98507, USA.
NIS Labs, Klamath Falls, OR 97601, USA.
J Inflamm Res. 2020 Feb 25;13:117-131. doi: 10.2147/JIR.S229446. eCollection 2020.
To compare three fractions of a medicinal mushroom blend (MMB), MyCommunity, on immune-activation, inflammation-regulation, and induction of biomarkers involved in regenerative functions.
A seventeen-species MMB was sequentially extracted: first, saline solution at ambient temperature, followed by re-extraction of the solids in ethanol, and finally resuspension of the homogenized ethanol-insoluble solids in cell-culture media. Fractions were tested on peripheral blood mononuclear cells from three healthy donors. Immunostaining, flow-cytometry, and Luminex protein-arrays measured immune-cell activation and cytokine response. Dose-responses for induction of the CD69 early activation marker and individual cytokine and growth-factor responses for each donor were evaluated. The CD69 and the combined cytokine and growth-factor results were subjected to Non-metric Multidimensional Scaling (NMDS) and multivariate ordination to aid interpretation of the aggregate immune response and pairwise permutational MANOVA on a distance-matrix to evaluate statistical differences between treatments on pooled data from all donors.
Differential effects were induced by water-soluble, ethanol-soluble, and insoluble immunomodulatory compounds of the MMB. The aqueous and ethanol fractions upregulated expression of CD69 on all tested cell types. Monocyte-activation was correlated with the ethanol fraction, while NKT and non-NK non-T cell-activation was more closely correlated with the aqueous fraction. The solid fraction was the most potent inducer of Tumor Necrosis Factor-α, as well as the anti-viral cytokines interferon-γ, MCP-1 (CCL-2), MIP-1α (CCL-3), and MIP-1β (CCL-4), and induced G-CSF and b-FGF-growth-factors involved in regenerative functions-and the anti-inflammatory cytokine IL-1ra.
The aqueous, ethanol, and insoluble compounds within MMB induced differential immune-activating, anti-inflammatory, and regenerative effects. This in vitro data suggests that, upon consumption, MMB may induce a concerted series of immunomodulatory events based on the differential solubility and bioavailability of the active constituents. These differential responses support both immune-activation and resolution of the host defense-induced inflammatory reactions, thus assisting a post-response return to homeostasis.
比较药用蘑菇混合物（MMB）MyCommunity的三个组分在免疫激活、炎症调节以及诱导参与再生功能的生物标志物方面的作用。
对包含17种菌种的MMB进行顺序提取：首先，在室温下用盐溶液提取，接着用乙醇对固体进行再提取，最后将匀化后的乙醇不溶性固体重悬于细胞培养基中。对来自三名健康供体的外周血单核细胞进行各组分测试。通过免疫染色、流式细胞术和Luminex蛋白阵列检测免疫细胞激活和细胞因子反应。评估诱导CD69早期激活标志物的剂量反应以及每位供体的单个细胞因子和生长因子反应。对CD69以及细胞因子和生长因子的综合结果进行非度量多维标度分析（NMDS）和多变量排序，以辅助解释总体免疫反应，并对距离矩阵进行成对置换多变量方差分析（MANOVA），以评估所有供体汇总数据中各处理之间的统计学差异。
MMB的水溶性、乙醇溶性和不溶性免疫调节化合物诱导了不同的效应。水相和乙醇相组分上调了所有测试细胞类型上CD69的表达。单核细胞激活与乙醇相组分相关，而自然杀伤T细胞（NKT）和非自然杀伤非T细胞激活与水相组分的相关性更强。固体相组分是肿瘤坏死因子-α以及抗病毒细胞因子干扰素-γ、单核细胞趋化蛋白-1（MCP-1，即CCL-2）、巨噬细胞炎性蛋白-1α（MIP-1α，即CCL-3）和巨噬细胞炎性蛋白-1β（MIP-1β，即CCL-4）的最有效诱导剂，并诱导了参与再生功能的粒细胞集落刺激因子（G-CSF）和碱性成纤维细胞生长因子（b-FGF）以及抗炎细胞因子白细胞介素-1受体拮抗剂（IL-1ra）。
MMB中的水相、乙醇相和不溶性化合物诱导了不同的免疫激活、抗炎和再生效应。这些体外数据表明，食用MMB后，基于活性成分的不同溶解度和生物利用度，可能会引发一系列协同的免疫调节事件。这些不同的反应既支持免疫激活，又有助于解决宿主防御诱导的炎症反应，从而协助在反应后恢复体内稳态。
