NF-κB and Cyclooxygenase-2 are Negatively Regulated by Glucocorticoid in C6 Glioma Cells
백봉숙, 김유정, 정해영,
소속 상세정보
백봉숙 ( Baek Bong-Sook )
부산대학교 약학대학
김유정 ( Kim You-Jung )
부산여자대학 피부미용과
정해영 ( Chung Hae-Young )
부산대학교 약학대학
KMID : 0603520010060040240
Abstract
Down-regulation of NF-B-dependent gene expression by glucocorticoids may be a key underlying mechanism for its anti-inflammatory and immunosuppressive effects, since the presence of NF-κB-responsive elements are required for expression of proinflammatory cytokines. It has been shown that glucocorticoid modulates gene expression of cyclooxygenase (COX-2) and inducible nitric oxide synthase (iNOS) by inhibiting NF-κB. It is also known that a synthetic glucocorticoid, dexamethasone (Dexa) inhibits NF-κB activation and increases the level of the inhibitor, I κB-α. In the present study, we attempted to delineate the molecular action of Dexa on the NF-κB-DNA binding activity and the modulation of NF-κB gene expression in C6 glioma cells. We also assessed the protein level of I κB-α to elucidate its action mechanism. Results showed that the NF-κB binding activity was inhibited in a dose-dependent manner by Dexa. Lipopoly-saccharide-induced luciferase activity in transfected cells with luciferase reporter plasmid containing NF-κB site of immunoglobulin κB promoer was also inhibited. Similarly, the NF-κB-dependent gene, COX-2 expression was effectively down-regulated by Dexa. A salient finding of our study was that the NF-κB inhibition by Dexa does not require a newly synthesized IκB-α, implying the involvement of some other regulatory process. Thus, our data provide a new insight on the molecular effect of glucocorticoid on NF-κB and COX-2 in C6 glioma cell, which can lead to a better understanding of its possible therapeutic usage.
키워드
NF-κB; COX-2; Glucocorticoid; C6 glioma cells; Dexamethasone
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