Harada Toshie, Miura Noriko N, Adachi Yoshiyuki, Nakajima Mitsuhiro, Yadomae Toshiro, Ohno Naohito
Laboratory for Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy & Life Science, Hachioji, Tokyo 192-0392, Japan.
J Interferon Cytokine Res. 2004 Aug;24(8):478-89. doi: 10.1089/1079990041689656.
Sparassis crispa Fr. is an edible/medicinal mushroom that recently became cultivable in Japan. SCG is a major 6-branched 1,3-beta-D-glucan in S. crispa showing antitumor activity. We recently found that the splenocytes from naive DBA/1 and DBA/2 mice strongly react with SCG to produce interferon-gamma (IFN-gamma). In this study, cytokines induced by SCG were screened and found to be IFN-gamma, tumor necrosis factor-alpha (TNF-alpha), granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin-12 (IL-12p70). The addition of recombinant murine GM-CSF (rMuGM-CSF) to spleen cell cultures from various strains of mice synergistically enhanced IFN-gamma, TNF-alpha and IL-12p70 in the presence of SCG. In contrast, neutralizing GM-CSF using anti-GM-CSF monoclonal antibody (mAb) significantly inhibited IFN-gamma, TNF-alpha, and IL-12p70 elicited by SCG. We conclude that GM-CSF is a key molecule for cytokine induction by beta-glucan, and GM-CSF induction by SCG is the specific step in DBA/2 mice in vitro.
皱盖乌芝(Sparassis crispa Fr.)是一种食药用真菌,最近在日本实现了人工栽培。SCG是皱盖乌芝中一种主要的6分支1,3-β-D-葡聚糖,具有抗肿瘤活性。我们最近发现,来自未接触过抗原的DBA/1和DBA/2小鼠的脾细胞与SCG强烈反应,产生干扰素-γ(IFN-γ)。在本研究中,对SCG诱导的细胞因子进行了筛选,发现其为IFN-γ、肿瘤坏死因子-α(TNF-α)、粒细胞-巨噬细胞集落刺激因子(GM-CSF)和白细胞介素-12(IL-12p70)。在存在SCG的情况下,向来自各种小鼠品系的脾细胞培养物中添加重组鼠GM-CSF(rMuGM-CSF)可协同增强IFN-γ、TNF-α和IL-12p70。相反,使用抗GM-CSF单克隆抗体(mAb)中和GM-CSF可显著抑制SCG诱导的IFN-γ、TNF-α和IL-12p70。我们得出结论,GM-CSF是β-葡聚糖诱导细胞因子的关键分子,并且SCG诱导GM-CSF是DBA/2小鼠体外的特定步骤。