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PSK对人外周血单个核细胞中基因表达的诱导及免疫调节细胞因子的产生

Induction of gene expression and production of immunomodulating cytokines by PSK in human peripheral blood mononuclear cells.

作者信息

Hirose K, Zachariae C O, Oppenheim J J, Matsushima K

机构信息

Laboratory of Molecular Immunoregulation, National Cancer Institute, Frederick, MD 21702-1201.

出版信息

Lymphokine Res. 1990 Winter;9(4):475-83.

PMID:2090874
Abstract

The protein-bound polysaccharide extracted from a fungus, PSK, has been used as a biological response modifier in the treatment of cancer patients in Japan for over ten years. Although the antitumor mechanism of PSK is not fully understood, host-mediated antitumor activity has been claimed to play a significant role. The administration of PSK to tumor-bearing rodents inhibited tumor growth and modulated immune responses. To clarify the potential immunomodulating activities of PSK, we examined the direct effect of PSK on cytokine gene expression and production in human peripheral blood mononuclear cells (PBMC) in vitro. As determined by Northern blotting, PSK was a potent inducer of gene expression for IL-1 alpha, IL-1 beta, IL-6, IL-8, tumor necrosis factor (TNF-alpha) and monocyte chemotactic and activating factor (MCAF), but not for IL-2 and lymphotoxin (LT). Expression of mRNA occurred at 1-3 hr in a dose dependent manner using from 5-400 micrograms/ml of PSK. Furthermore, these cytokines were also produced in response to PSK as detected by ELISA, RIA or bioassays. We speculate that these cytokines may mediate immunoenhancing actions of PSK in vivo.

摘要

从一种真菌中提取的蛋白结合多糖PSK,在日本作为生物反应调节剂用于癌症患者的治疗已有十多年。尽管PSK的抗肿瘤机制尚未完全明确,但据认为宿主介导的抗肿瘤活性起着重要作用。给荷瘤啮齿动物施用PSK可抑制肿瘤生长并调节免疫反应。为了阐明PSK潜在的免疫调节活性,我们在体外研究了PSK对人外周血单个核细胞(PBMC)中细胞因子基因表达和产生的直接影响。通过Northern印迹法测定,PSK是IL-1α、IL-1β、IL-6、IL-8、肿瘤坏死因子(TNF-α)和单核细胞趋化及激活因子(MCAF)基因表达的有效诱导剂,但不是IL-2和淋巴毒素(LT)的诱导剂。使用5 - 400微克/毫升的PSK,mRNA表达在1 - 3小时以剂量依赖方式出现。此外,通过ELISA、RIA或生物测定法检测发现,这些细胞因子也因PSK而产生。我们推测这些细胞因子可能在体内介导PSK的免疫增强作用。

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Lymphokine Res. 1990 Winter;9(4):475-83.
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