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Spirulina lipopolysaccharides inhibit tumor growth in a Toll-like receptor 4-dependent manner by altering the cytokine milieu from interleukin-17/interleukin-23 to interferon-γ

  • Authors:
    • Hiromi Okuyama
    • Akira Tominaga
    • Satoshi Fukuoka
    • Takahiro Taguchi
    • Yutaka Kusumoto
    • Shiro Ono
  • View Affiliations / Copyright

    Affiliations: Laboratory of Immunology, Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi, Osaka 584-8540, Japan, Laboratory of Human Health and Medical Science, Graduate School of Kuroshio Science, and Department of Molecular Biology and Cellular Biology, Kochi Medical School, Kochi University, Nankoku, Kochi 783-8505, Japan, Health Technology Research Center, National Institute of Advanced Industrial Science and Technology (AIST), Takamatsu, Kagawa 761-0395, Japan
    Copyright: © Okuyama et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 684-694
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    Published online on: January 2, 2017
       https://doi.org/10.3892/or.2017.5346
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Abstract

Th17 cells and the cytokine they produce, interleukin (IL)-17, play an important role in tumor progression in humans and in mice. IL-6 and IL-23 are critical cytokines for the differentiation and propagation of Th17 cells, respectively. Bacterial lipopolysaccharides (LPS) are known to stimulate immune cells to produce such inflammatory cytokines. Contrary to Escherichia coli (E. coli) LPS, LPS from Spirulina has low toxicity and barely induces in vivo production of IL-6 and IL-23 in mice. We examined the antitumor effects of Spirulina LPS compared to E. coli LPS in an MH134 hepatoma model. Administration of Spirulina LPS suppressed tumor growth in C3H/HeN mice, but not in Toll-like receptor 4 (TLR4)-mutant C3H/HeJ mice, by reducing serum levels of IL-17 and IL-23, while increasing interferon (IFN)-γ levels. The antitumor activity and IFN-γ production were mediated by T cells. Moreover, in vitro experiments showed that Spirulina LPS impaired the antigen-presenting function that supports the generation of IL-17-producing cells in a toll-like receptor (TLR)4-dependent manner. Of note, injection of anti-IL-17 antibody in tumor-bearing C3H/HeN mice in the absence of Spirulina LPS markedly suppressed tumor growth and augmented IFN-γ responses. Thus, our results support the notion that IFN-γ and IL-17/IL-23 mutually regulate Th17 and Th1 responses in tumor-bearing hosts, and Spirulina LPS modulates the balance of the IFN-γ-IL-17/IL-23 axis towards IFN-γ production, which leads to tumor inhibition. Furthermore, Spirulina LPS effectively inhibited the spontaneous development of mammary tumors. This study has important implications for the exploitation of TLR-based immunomodulators for cancer immunotherapy.
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Copy and paste a formatted citation
Spandidos Publications style
Okuyama H, Tominaga A, Fukuoka S, Taguchi T, Kusumoto Y and Ono S: Spirulina lipopolysaccharides inhibit tumor growth in a Toll-like receptor 4-dependent manner by altering the cytokine milieu from interleukin-17/interleukin-23 to interferon-γ. Oncol Rep 37: 684-694, 2017.
APA
Okuyama, H., Tominaga, A., Fukuoka, S., Taguchi, T., Kusumoto, Y., & Ono, S. (2017). Spirulina lipopolysaccharides inhibit tumor growth in a Toll-like receptor 4-dependent manner by altering the cytokine milieu from interleukin-17/interleukin-23 to interferon-γ. Oncology Reports, 37, 684-694. https://doi.org/10.3892/or.2017.5346
MLA
Okuyama, H., Tominaga, A., Fukuoka, S., Taguchi, T., Kusumoto, Y., Ono, S."Spirulina lipopolysaccharides inhibit tumor growth in a Toll-like receptor 4-dependent manner by altering the cytokine milieu from interleukin-17/interleukin-23 to interferon-γ". Oncology Reports 37.2 (2017): 684-694.
Chicago
Okuyama, H., Tominaga, A., Fukuoka, S., Taguchi, T., Kusumoto, Y., Ono, S."Spirulina lipopolysaccharides inhibit tumor growth in a Toll-like receptor 4-dependent manner by altering the cytokine milieu from interleukin-17/interleukin-23 to interferon-γ". Oncology Reports 37, no. 2 (2017): 684-694. https://doi.org/10.3892/or.2017.5346
Copy and paste a formatted citation
x
Spandidos Publications style
Okuyama H, Tominaga A, Fukuoka S, Taguchi T, Kusumoto Y and Ono S: Spirulina lipopolysaccharides inhibit tumor growth in a Toll-like receptor 4-dependent manner by altering the cytokine milieu from interleukin-17/interleukin-23 to interferon-γ. Oncol Rep 37: 684-694, 2017.
APA
Okuyama, H., Tominaga, A., Fukuoka, S., Taguchi, T., Kusumoto, Y., & Ono, S. (2017). Spirulina lipopolysaccharides inhibit tumor growth in a Toll-like receptor 4-dependent manner by altering the cytokine milieu from interleukin-17/interleukin-23 to interferon-γ. Oncology Reports, 37, 684-694. https://doi.org/10.3892/or.2017.5346
MLA
Okuyama, H., Tominaga, A., Fukuoka, S., Taguchi, T., Kusumoto, Y., Ono, S."Spirulina lipopolysaccharides inhibit tumor growth in a Toll-like receptor 4-dependent manner by altering the cytokine milieu from interleukin-17/interleukin-23 to interferon-γ". Oncology Reports 37.2 (2017): 684-694.
Chicago
Okuyama, H., Tominaga, A., Fukuoka, S., Taguchi, T., Kusumoto, Y., Ono, S."Spirulina lipopolysaccharides inhibit tumor growth in a Toll-like receptor 4-dependent manner by altering the cytokine milieu from interleukin-17/interleukin-23 to interferon-γ". Oncology Reports 37, no. 2 (2017): 684-694. https://doi.org/10.3892/or.2017.5346
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