Inhibition of TNF-α, Induced Cytokine and Adhesion Molecule
Inhibition of TNF-α, Induced Cytokine and Adhesion Molecule
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TNF-α、诱导细胞因子和粘附分子的抑制
DOI：
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发表时间：
2001
影响因子：
--
通讯作者：
M. Horiuchi
中科院分区：
文献类型：
--
作者：
N. Tomita;R. Morishita;S. Tomita;Y. Kaneda;J. Higaki;T. Ogihara;M. Horiuchi
某些细胞因子和粘附分子的激活被认为与实验肾小球肾炎和人类肾小球肾炎的发病机制有关。在这项研究中，我们通过使用转录因子诱饵寡脱氧核苷酸（ODN）来阻断 NFĸB 与其靶基因的启动子位点结合，检查转录因子核因子 ĸB (NFĸB) 是否介导这些与系膜细胞炎症反应有关的基因的表达。我们假设 NFĸB 诱饵 ODN 可以抑制 TNF-α 诱导的细胞因子和粘附分子的协同激活。 TNF-α 诱导的 NFκB 结合活性增加被 NFκB 诱饵 ODN 有效阻断。 TNF-α 刺激 CAT 表达，转染 NFκB 显着抑制 CAT 表达，但不被乱序诱饵 ODN 抑制。重要的是，通过 RT-PCR 评估，NFĸB（而非乱序诱饵 ODN）显着减弱了 TNF-α 诱导的 IL-1α、IL-1β、IL-6、ICAM-1 和 VCAM-1 RNA 和蛋白质水平的增加。此外，NFκB诱饵ODN的体内转染抑制了TNF-α注射诱导的这些细胞因子和粘附分子的表达。这些结果提出了一种治疗肾小球肾炎的新治疗策略，即使用诱饵 ODN 阻断 NFκB 的结合，抑制关键细胞因子和粘附分子的协调反式激活，从而抑制炎症过程。
Activation of certain cytokines and adhesion molecules has been postulated being involved in the pathogenesis of experimental and human glomerulonephritis. In this study, we examined whether the transcription factor, nuclear factor ĸB (NFĸB), mediated the expression of these genes involved with the inflammatory response of mesangial cells by using transcription factor decoy oligodeoxynucleotides (ODN) to block NFĸB binding to the promoter site of its target genes. We hypothesized that the NFĸB decoy ODN can inhibit the coordinated activation of cytokines and adhesion molecules induced by TNF-α. Increased binding activity of NFĸB induced by TNF-α was effectively blocked by the NFĸB decoy ODN. TNF-α stimulated CAT expression, which was significantly inhibited by transfection of NFĸB, but not by scrambled decoy ODN. Of importance, NFĸB, but not scrambled decoy ODN, significantly attenuated the increase in RNA and protein levels of IL-1α, IL-1β, IL-6, ICAM-1 and VCAM-1 induced by TNF-α assessed by RT-PCR. Moreover, in vivo transfection of NFĸB decoy ODN inhibited expressions of these cytokines and adhesion molecules induced by TNF-α injection. These results suggest a novel therapeutic strategy for the treatment of glomerulonephritis using decoy ODN to block the binding of NFĸB, inhibiting the coordinated transactivation of the key cytokines and adhesion molecules, and thereby suppressing the inflammatory process.
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DOI：
10.1152/ajprenal.1998.275.2.f278
发表时间：
1998
期刊：
The American journal of physiology
影响因子：
--
作者：
Tomita,N;Horiuchi,M;Tomita,S;Gibbons,GH;Kim,JY;Baran,D;Dzau,VJ
通讯作者：
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影响因子：
15.9
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通讯作者：
SCHLONDORFF, D
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影响因子：
20.1
作者：
Tomita,S;Tomita,N;Yamada,T;Zhang,L;Kaneda,Y;Morishita,R;Ogihara,T;Dzau,VJ;Horiuchi,M
通讯作者：
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DOI：
10.1172/jci118156
发表时间：
1995
期刊：
The Journal of clinical investigation.
影响因子：
--
作者：
Yamada,T;Horiuchi,M;Morishita,R;Zhang,L;Pratt,RE;Dzau,VJ
通讯作者：
Dzau,VJ
DOI：
10.1073/pnas.92.13.5855
发表时间：
1995-06-20
影响因子：
11.1
作者：
MORISHITA, R;GIBBONS, GH;DZAU, VJ
通讯作者：
DZAU, VJ