Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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Inhibition of p65 Nuclear Translocation by Radicicol, Heat Shock Protein Inhibitor

  • Kim, Sang-Gyu (Graduate School, Chosun University College of Medicine) ;
  • Jeon, Young-Jin (Department of Pharmacology, Chosun University College of Medicine) ;
  • Lee, Seog-Ki (Department of Thoracic and Cardiovascular Surgery, Chosun University College of Medicine)
  • Published : 2005.12.01
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Abstract

We demonstrate that radicicol, a macrocyclic antifungal antibiotic originally isolated from Monosporium bonorden, inhibits LPS-induced expression of iNOS gene in RAW 264.7 cells. Treatment of peritoneal macrophages and RAW 264.7 cells with radicicol inhibited LPS-stimulated nitric oxide production in a dose-related manner. Immunohistochemical staining of iNOS and RTPCR analysis showed that the decrease of NO was due to the inhibition of iNOS gene expression in RAW 264.7 cells. Immunostaining of p65, EMSA, and reporter gene assay showed that radicicol inhibited $NF-\kappa/Rel$ nuclear translocation. DNA binding, and transcriptional activation, respectively. Collectively, these series of experiments indicate that radicicol inhibits iNOS gene expression by blocking $NF-\kappa/Rel$ nuclear translocation. Due to the critical role that NO release plays in mediating inflammatory responses, the inhibitory effects of radicicol on iNOS suggest that radicicol may represent a useful anti-inflammatory agent.

Keywords

References

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