Radicicol에 의한 65 단백질의 핵내 이동 억제에 관한 연구 : p65단백질의 핵내 이동에 관한 연구

Abstract

In this study, radicicol, a macrocyclic antifungal antibiotics 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. Immunohisto-chemical staining of iNOS and RT-PCR analysis showed that the decrease of NO was due to the inhibition of iNOS gene expression. Immunostaining of p65, electrophoretic mobility sift assay, and reporter gene assay showed that radicicol inhibited NF-k/Rel nuclear translocation, DNA binding, and transcriptional activation, respectively. Collectively, the experiments indicate that radicicol inhibits iNOS gene expression by blocking NF-k/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. In this study, radicicol, a macrocyclic antifungal antibiotics 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. Immunohisto-chemical staining of iNOS and RT-PCR analysis showed that the decrease of NO was due to the inhibition of iNOS gene expression. Immunostaining of p65, electrophoretic mobility sift assay, and reporter gene assay showed that radicicol inhibited NF-k/Rel nuclear translocation, DNA binding, and transcriptional activation, respectively. Collectively, the experiments indicate that radicicol inhibits iNOS gene expression by blocking NF-k/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.