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Protein-bound polysaccharide K augments IL-2 production from murine mesenteric lymph node CD4+ T cells by modulating T cell receptor signaling

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Abstract

The protein-bound polysaccharide isolated from basidiomycetes (PSK), a biological response modifier, has been used as immunotherapeutic agent for the treatment of cancers. It has been demonstrated previously that PSK activates various types of immune cells in vitro, and orally administrated PSK activates anti-tumor CD4+ T cell response in mesenteric lymph nodes (MLNs). The detailed mechanism of action of PSK, however, has not been elucidated yet. The objective of the present study was to clarify the molecular mechanism of immunopotentiating effects of PSK using primary culture of the MLN CD4+ T cells. T cell receptor (TCR) stimulation-induced interleukin-2 production from MLN CD4+ T cells was significantly augmented by PSK in a concentration-dependent manner, and the augmentation was reflected at mRNA level. Furthermore, PSK augmented transcriptional activities of nuclear factor of activated T cells and activator protein 1, and phosphorylation of extracellular signal-regulated kinase 1/2 and linker for activation of T cells induced by TCR stimulation, whereas PSK had no influences without TCR stimulation. Collectively, the results indicate that PSK augments activation of MLN CD4+ T cells, probably by modulating the TCR signaling, and provide important knowledge for the elucidation of the true target molecule(s) of PSK.

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Abbreviations

ANOVA:

Analysis of variance

AP1:

Activator protein 1

CRE:

cAMP-response element

ERK:

Extracellular signal-regulated kinase

GALT:

Gut-associated lymphoid tissue

GAPDH:

Glyseraldehyde-3-phosphate dehydrogenase

IFN-g:

Interferon-gamma

IL:

Interleukin

LAT:

Linker for activation of T cells

LPS:

Lipopolysaccharide

MLN:

Mesenteric lymph node

NF-AT:

Nuclear factor of activated T cells

Pam3CSK4:

Pam3Cys-Ser-(Lys)4

PMA:

Phorbol 12-myristate 13-acetate

RT-PCR:

Reverse transcriptase-polymerase chain reaction

TCR:

T cell receptor

TLR:

Toll-like receptor

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Acknowledgments

The authors thank Takao Ando for his comment on the manuscript and Shunsuke Ito for his technical assistance.

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Authors and Affiliations

  1. Biomedical Research Laboratories, Kureha Corporation, 3-26-2 Hyakunin-cho, Shinjuku-ku, Tokyo, 169-8503, Japan

    Hirobumi Asai, Hiroko Iijima, Kenichi Matsunaga & Yoshiharu Oguchi

  2. Department of Surgery, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake, Toyoake, Aichi, 470-1192, Japan

    Hidetoshi Katsuno & Koutaro Maeda

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  1. Hirobumi Asai
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  2. Hiroko Iijima
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  3. Kenichi Matsunaga
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Correspondence to Hirobumi Asai.

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Asai, H., Iijima, H., Matsunaga, K. et al. Protein-bound polysaccharide K augments IL-2 production from murine mesenteric lymph node CD4+ T cells by modulating T cell receptor signaling. Cancer Immunol Immunother 57, 1647–1655 (2008). https://doi.org/10.1007/s00262-008-0498-1

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