| The Effect of DA-6034, a Synthetic Derivative of Flavonoid, on NF-κB Activity Stimulated with Lipopolysaccharide and Tumor Necrosis actor-α in Human Colonic Epithelial Cell Line |
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Ji Won Kim, Yong-Jin Jung, Ji Bong Jeong, Byeong Gwan Kim, Kook Lae Lee, Joo Sung Kim, Hyun Chae Jung, In Sung Song |
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Department of Internal Medicine, Seoul National University Boramae Hospital, Department of Internal Medicine, College of Medicine, Seoul National University, Seoul, Korea
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| 플라보노이드 합성 유도체인 DA-6034가 인간 대장 점막 상피 세포주에서 Lipopolysaccharide 및 Tumor Necrosis Factor-α 자극에 의한 NF-κB의 활성화에 미치는 영향 |
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김지원, 정용진, 정지봉, 김병관, 이국래, 김주성, 정현채, 송인성 |
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서울대학교 보라매병원, 서울대학교 의과대학 내과학교실 |
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| Abstract |
Background/Aims
The nuclear factor-κB (NF-κB) is associated with expression of proinflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-8 (IL-8). DA-6034, a derivative of flavonoid, has shown a potent anti-inflammatory effect in IBD animal model. The aim of this study was to characterize the anti-inflammatory activity of DA-6034 in terms of regulation of NF-κB. Methods: HT-29 cells were stimulated with lipopolysaccharide (LPS) or TNF-α alone or pretreated with DA-6034. The influence of DA-6034 on NF-κB DNA binding activity and inhibitory protein κB (IκB) activity was determined using an electrophoretic mobility shift assay (EMSA) and Western blot analysis. The RT-PCR method was used to determine the degree of gene expression of TNF-α and IL-8. Production of TNF-α and IL-8 protein was measured by ELISA. Results: DA-6034 prevented NF-κB activation stimulated with LPS and TNF-α and inhibited LPS- and TNF-α-induced IκB degradation. LPS-induced TNF-α mRNA expression and TNF-α-induced IL-8 mRNA expression were significantly decreased by DA-6034 pretreatment as compared to the absence of DA-6034 pretreatment. Conclusions: These results suggest that the inhibitory effect of DA-6034 on the production of TNF-α in LPS-stimulated and IL-8 in TNF-α-stimulated HT-29 cells may involve transcription regulation by suppression of NF-κB activation by interfering with IκB degradation. (Intest Res 2005; 3:38-47) |
| Key Words:
IBD, DA-6034, NF-κB, IκB |
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