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DA-9601, a standardized extract of Artemisia asiatica, blocks TNF-α-induced IL-8 and CCL20 production by inhibiting p38 kinase and NF-κ-B pathways in human gastric epithelial cells

查看全文 作　　者：Suck-Chei [1]Choi;Eun-Ju [2]Choi;Hyun-Mee [3]Oh;SungGa [3]Lee;Jeong-Kun [1]Lee;Meung-Su [1]Lee;Yong-Il [1]Shin;Suck-Jun [4]Choi;Jeong-Ryong [2]Chae;Kang-Min [5]Lee;Won-Jung [6]Lee;Jae-Sik [6]Park;Chang-Yell [7]Shin;Tae-Young [7]Oh;Chang-Duk [3]Jun 高影响力作者 机构地区：[1]Digestive Disease Research Institute,Wonkwang University School of Medicine, Iksan, Chonbuk 570-749, Korea;[2]Department Physical Education,Kunsan National University, Chonbuk 573-701, Korea;[3]Department of Life Science,Gwangju Institute of Science and Technology, Gwangju 500-712, Korea;[4]Department of Leisure Sports,Wonkwang Health Science College, Iksan, Chonbuk 570-749, Korea;[5]Division of Biological Sciences,College of Natural Science, Chonbuk National University, Jeonju, Chonbuk 561-756, Korea;[6]Department of Physiology,Kyungpook National University School of Medicine, Taegu 700-422, Korea;[7]Research Institute,Dong-A Pharmaceutical Co. Ltd., Yongin 449-905, Korea高影响力机构 出　　处：《World Journal of Gastroenterology》索引2006年第12卷第30期,共9页高影响力期刊 基　　金：Supported by grants from the Korea Health 21 R&D Project, Ministry of Health and Welfare, No.01-PJ3-PG6-01GN09-003, and the Korea Food and Drug Administration, No. 05142-620 摘　　要：AIM: To investigate whether, or how, DA-9601, which is a new gastroprotective agent, inhibits TNF-α-induced inflammatory signals in gastric epithelial AGS cells. METHODS: Cell viability was determined by MTT assay. IL-8 and CCL20 promoter activities were determined by a luciferease reporter gene assay. NF-κB-dependent transcriptional activity was determined by I-κBαdegradation, NF-κB p65 nuclear translocation and a luciferase activity assay. IL-8 and CCL20 gene expression and protein secretion were determined by RT-PCR and an enzymelinked immunosorbent assay (ELISA). Total and phos-phorylated forms of mitogen-activated protein kinases (MAPKs) were determined by Western blot. RESULTS: Treatment of AGS cells with DA-9601 reduced TNF-α-induced IL-8 and CCL20 promoter activities, as well as their gene expression and protein release. TNF-αalso induced NF-κB-dependent transcriptional activity in AGS cells. In contrast, in cells treated with DA-9601, TNF-α-induced NF-κB activity was significantly blocked. Although all three MAP kinase family members were phosphorylated in response to TNF-α, a selective inhibitor of p38 kinase SB203580 only could inhibit both NF-κB-dependent transcriptional activity and IL-8 and CCL20 production, suggesting a potential link between p38 kinase and NF-κB-dependent pathways in AGS cells. Interestingly, DA-9601 also selectively inhibited p38 kinase phosphorylation induced by TNF-α. CONCLUSION: DA-9601 blocked TNF-α-mediated inflammatory signals by potentially modulating the p38 kinase pathway and/or a signal leading to NF-κBdependent pathways in gastric epithelial cells. 关 键 词：DA-9601 艾属 NF-κB 胃癌 中药治疗
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