Antimetastatic Effect of an Immunomodulatory Arabinomannan Extracted from Mycobacterium tuberculosis Strain Aoyama B, Z-100, through the Production of Interleukin-12
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- Oka Hideki
- Central Research Laboratories, Zeria Pharmaceutical Co., Ltd.
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- Shiraishi Yumiko
- Central Research Laboratories, Zeria Pharmaceutical Co., Ltd.
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- Sasaki Hidetaka
- Central Research Laboratories, Zeria Pharmaceutical Co., Ltd.
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- Yoshinaga Koji
- Central Research Laboratories, Zeria Pharmaceutical Co., Ltd.
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- Emori Yutaka
- Central Research Laboratories, Zeria Pharmaceutical Co., Ltd.
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- Takei Mineo
- Central Research Laboratories, Zeria Pharmaceutical Co., Ltd.
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抄録
In this study, the role of interleukin (IL)-12 on the antimetastatic effect of Z-100 was investigated using wild-type C57BL/6 mice or IL-12p40 knockout (IL-12p40 KO) mice inoculated with highly metastatic B16F10 melanoma. When C57BL/6 mice were inoculated with B16F10 melanoma (2×105 cells/mouse i.v.), Z-100 (10 mg/kg i.p.) significantly suppressed the pulmonary metastasis of B16F10 melanoma 14 d after tumor inoculation. On the other hand, the antimetastatic effect of Z-100 was not observed in IL-12p40 KO mice inoculated with B16F10 melanoma. These results indicate that IL-12 is essentially required for the appearance of the antimetastatic effect of Z-100. Since helper T (Th) 2 cell responses have been reported to have a role in tumor metastasis, the regulatory effect of Z-100 on the immune balance of Th1/Th2 cell responses was investigated. In both C57BL/6 mice and IL-12p40 KO mice bearing B16F10 melanoma, Th1 cytokine production (IL-2, interferon-γ) was significantly suppressed as compared with those in normal mice. On the other hand, Th2 cytokine production (IL-4, IL-10) in these mice was increased. The administration of Z-100 (10 mg/kg i.p.) in C57BL/6 mice bearing B16F10 melanoma improved the balance of Th1/Th2 cell responses from the Th2-dominant state to the normal state. However, the improvement of Th1/Th2 cell responses by Z-100 was not observed in IL-12p40 KO mice bearing the same tumors. In addition, Z-100 significantly increased IL-12 production by macrophages in a concentration-dependent manner, while Z-100 significantly decreased IL-10 production by these cells in vitro. These results suggested that up-regulation of IL-12 production and down-regulation of IL-10 production by Z-100 are related to the improvement of Th1/Th2 cell responses from the Th2-dominant state to the normal state, which resulted in suppression of tumor metastasis.
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 26 (9), 1336-1341, 2003
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390001204628497536
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- NII論文ID
- 110003608598
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- NII書誌ID
- AA10885497
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- COI
- 1:STN:280:DC%2BD3svhtFalsg%3D%3D
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- ISSN
- 13475215
- 09186158
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- NDL書誌ID
- 6658310
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- PubMed
- 12951482
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可