Category Archives: Cytokines

Stimulation of interferon-gamma-induced human myelogenous leukemic cell differentiation by high molecular weight PSK subfraction.

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Anticancer Res. 1990 Jan-Feb;10(1):55-8.

Kim F, Sakagami H, Tanuma S, Konno K.

First Department of Biochemistry, School of Medicine, Showa University, Tokyo, Japan.

Abstract

PSK, a protein-bound polysaccharide extracted from the mycelia of Coriolus versicolor (Fr.) Quel, stimulated tumor

necrosis factor-induced cytotoxicity against mouse L-929 fibroblast. PSK also stimulated interferon-gamma-induced

differentiation of human myelogenous leukemic U-937 and THP-1 cells. The differentiated cells had higher proportions of

cells that expressed NBT-reducing activity and alpha-naphthyl acetate esterase activity. Among four PSK subfractions, the

highest molecular weight fraction (MW greater than 200 kD) had the most potent stimulating activity. This is the first report

regarding direct PSK modulation of cytokine action.

PMID: 2110432 [PubMed – indexed for MEDLINE]

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Usefulness of immunomodulators for maturation of dendritic cells.

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Int J Oncol. 2004 Aug;25(2):453-9.

Ogihara T, Iinuma H, Okinaga K.

Department of Surgery, Teikyo University School of Medicine, Tokyo 173-0003, Japan.

Abstract

Biological response modifiers (BRMs) augment the cytotoxic activity of various effector cells by the induction of multiple

cytokines and suppression of immunosuppressive factors. BRMs are used extensively in adjuvant therapy for gastric

cancer in Japan. In dendritic cell (DC)-based vaccine therapy, the quality of DCs is important in inducing strong antitumor

immunity. A good manufacturing practice (GMP) grade agent for DCs maturation is desirable for safety. Here we report

the effects of two BRMs, OK432 and PSK, which are GMP grade agents for the functional maturation of DCs. OK432 and

PSK were examined in vitro, and compared with lipopolysaccharide (LPS) and a cytokine cocktail (IL-1beta, TNF-alpha,

IL-6 and PGE2). In the immunophenotypical analysis, the expression of CD80 and CD83 of DCs stimulated with OK-432

increased significantly compared with PSK and medium, and this up-regulation was the same as levels of DCs stimulated

with cytokine cocktail. DCs stimulated with OK-432 showed significantly higher production of IL-12 and Th1-type cytokines

(IL-2 and IFN-gamma) compared with DCs stimulated with LPS or cytokine cocktail. OK-432 stimulated DCs could induce

the significantly high level of cytotoxic T cell activity compared with PSK-stimulated or unstimulated DCs. These results

suggest that OK432 is a GMP-grade reagent that promotes functional maturation of DCs and could be applied in

DC-based vaccinations.

PMID: 15254744 [PubMed – indexed for MEDLINE]

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Activation of human natural killer cells by the protein-bound polysaccharide PSK

The protein-bound polysaccharide PSK was tested for the ability to activate human natural killer (NK) cells. When blood lymphocytes and purified CD3-CD16 รท large granular lymphocytes (LGL) were treated in vitro overnight with PSK, they demonstrated enhanced NK cell activity against K562. The PSK-activated killer cells also lysed NK-resistant targets and freshly isolated autologous and allogeneic tumor cells. The PSK effect was observed with concentrations that could be obtained in the blood of cancer patients receiving oral administration of PSK. PSK-induced enhancement of NK activity was not abrogated by monoclonal antibodies (mAb) that neutralized interferon (IFN)o~, IFN3,, or interleukin-2 (IL-2). In addition, mAb reactive with p55 (~ chain) or p75 (/3 chain) glycoproteins of IL-2 receptors had no effects on PSK-enhanced NK activity even when used simultaneously. These results indicate that the PSK could activate human NK cells independently of IFN and IL-2/IL-2R systems.

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