Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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Pretreatment of Macrophages with Paclitaxel Inhibits iNOS Expression

  • Li Mei-Hong (Department of Pharmacology, Chosun University College of Medicine) ;
  • Kang Jong-Soon (Korea Research Institute of Bioscience and Biotechnology) ;
  • Kim Hwan-Mook (Korea Research Institute of Bioscience and Biotechnology) ;
  • Jeon Young-Jin (Department of Pharmacology, Chosun University College of Medicine)
  • Published : 2006.06.01
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Abstract

We demonstrate that paclitaxel, an antitumor agent derived from yew tree, inhibits LPS-induced expression of iNOS gene in RAW 264.7 cells. Previously, paclitaxel has been known to induce iNOS gene expression in macrophages. However, in this report we described that the pre-treatment of macrophages with paclitaxel ($0.1{\mu}M$) for 8 h inhibited LPS-induced iNOS gene expression. Pretreatment of RAW 264.7 cells with paclitaxel significantly inhibited LPS-stimulated nitric oxide (NO) production. Western immunoblot of iNOS and RT-PCR analysis showed that the decrease of NO was due to the inhibition of iNOS gene expression in RAW 264.7 cells. Immunocytochemical staining of iNOS further confirmed that pretreatment of macrophages with paclitaxel inhibited macrophage activation. Electrophoretic mobility shift assay showed that paclitaxel inhibited $NF-_{\kappa}/Rel$ DNA binding. Collectively, these series of experiments indicate that paclitaxel inhibits iNOS gene expression by blocking $NF-_{\kappa}B/Rel$ activation.

Keywords

References

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