ONO-4007, a synthetic lipid A analog, induces Th1-type immune response in tumor eradication and restores nitric oxide production by peritoneal macrophages

  • Authors:
    • Kazuhiro Matsushita
    • Yasuhiro Kuramitsu
    • Yoichi Ohiro
    • Ichizo Kobayashi
    • Tae Watanabe
    • Masanobu Kobayashi
    • Masuo Hosokawa
  • View Affiliations

  • Published online on: August 1, 2003     https://doi.org/10.3892/ijo.23.2.489
  • Pages: 489-493
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Abstract

We have reported that ONO-4007, a novel synthetic lipid A derivative with low toxic activities, produced large amount of tumor necrosis factor (TNF)-α selectively in the tumor tissues and brought about complete cures in about 60% of rats bearing TNF-α sensitive KDH-8 cells, which also secreted a large amount of transforming growth factor (TGF)-β. In our present study, to explore ONO-4007 induced Th1-type immune response, we investigated the mRNA expression of interferon (IFN)-γ, Interleukin (IL)-1β, IL-6, IL-10, IL-12 in KDH-8 bearing rats. We next examined the nitric oxide (NO) production. We found that IFN-γ, IL-1β, IL-6 and IL-12 mRNA expression of the tumor tissue were higher in the ONO-4007 treated rats than in phosphate buffer saline (PBS) treated rats. Western blotting also revealed that IL-12 protein production was increased. NO production from peritoneal macrophages were suppressed in tumor-bearing rats, but ONO-4007 restored it up to the normal level. These results suggest that ONO-4007 induces and restores Th1-type immune response through cytokine production cascade, followed by initial TNF-α production, eventually leading to tumor eradication.

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August 2003
Volume 23 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Matsushita K, Kuramitsu Y, Ohiro Y, Kobayashi I, Watanabe T, Kobayashi M and Hosokawa M: ONO-4007, a synthetic lipid A analog, induces Th1-type immune response in tumor eradication and restores nitric oxide production by peritoneal macrophages. Int J Oncol 23: 489-493, 2003
APA
Matsushita, K., Kuramitsu, Y., Ohiro, Y., Kobayashi, I., Watanabe, T., Kobayashi, M., & Hosokawa, M. (2003). ONO-4007, a synthetic lipid A analog, induces Th1-type immune response in tumor eradication and restores nitric oxide production by peritoneal macrophages. International Journal of Oncology, 23, 489-493. https://doi.org/10.3892/ijo.23.2.489
MLA
Matsushita, K., Kuramitsu, Y., Ohiro, Y., Kobayashi, I., Watanabe, T., Kobayashi, M., Hosokawa, M."ONO-4007, a synthetic lipid A analog, induces Th1-type immune response in tumor eradication and restores nitric oxide production by peritoneal macrophages". International Journal of Oncology 23.2 (2003): 489-493.
Chicago
Matsushita, K., Kuramitsu, Y., Ohiro, Y., Kobayashi, I., Watanabe, T., Kobayashi, M., Hosokawa, M."ONO-4007, a synthetic lipid A analog, induces Th1-type immune response in tumor eradication and restores nitric oxide production by peritoneal macrophages". International Journal of Oncology 23, no. 2 (2003): 489-493. https://doi.org/10.3892/ijo.23.2.489