Amelioration of Acute Inflammation by Systemic Administration of a Cell-Permeable Peptide Inhibitor of NF-κB Activation
Amelioration of Acute Inflammation by Systemic Administration of a Cell-Permeable Peptide Inhibitor of NF-κB Activation
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DOI：
10.1002/art.20960
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发表时间：
2005-03-01
影响因子：
--
通讯作者：
Ghosh, Sankar
中科院分区：
文献类型：
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作者：
di Meglio, Paola;Ianaro, Angela;Ghosh, Sankar
Objective.我们使用的实验模型，角叉菜胶诱导的爪水肿，在小鼠中的炎症，研究NEMO结合域（NBD）肽，它阻止激活的诱导型转录因子NF-κ B的抑制作用。通过向小鼠左后爪中足底下注射1%葡聚糖-角叉菜胶诱导爪水肿。在角叉菜胶注射后立即腹膜内给予测试剂。足垫厚度增加被认为是水肿。在一些实验中，小鼠被杀死，并且爪被移除用于组织学和分子生物学分析。通过电泳迁移率变动分析评价核提取物中NF-κ B DNA结合活性。免疫印迹法检测NF-κ B调节的环氧合酶2（考克斯-2）蛋白表达，逆转录聚合酶链反应扩增肿瘤坏死因子α（TNF α）mRNA。我们发现全身施用NBD肽显著抑制发炎小鼠爪中的水肿形成和细胞浸润。这种抗炎活性很可能是由于抑制炎症组织中促炎介质如TNF α和考克斯-2的表达。这些研究进一步确立了NF-κ B作为炎症治疗的靶点，并为NBD肽作为炎症性疾病的可能治疗剂的用途提供了支持。
Objective. We used an experimental model of inflammation in mice, carrageenan-induced paw edema, to study the antiinflammatory effects of the NEMO-binding domain (NBD) peptide, which blocks activation of the inducible transcription factor NF-kappa B.Methods. Paw edema was induced by subplantar injection of 1% lambda-carrageenan into the mouse left hind paw. Test agents were given intraperitoneally immediately after carrageenan injection. The increase in footpad thickness was considered to be edema. In some experiments, the mice were killed and the paws were removed for histologic and molecular biology analysis. NF-kappa B DNA binding activity was evaluated in nuclear extracts by electrophoretic mobility shift assays. The expression levels of NF-kappa B-regulated cyclooxygenase 2 (COX-2) protein and tumor necrosis factor alpha (TNF alpha) messenger RNA (mRNA) were evaluated by immunoblot analysis and polymerase chain reaction amplification of reverse-tran scribed mRNA, respectively.Results. We found that systemically administered NBD peptide significantly inhibited edema formation and cellular infiltration in inflamed mouse paws. This antiinflammatory activity was most likely due to inhibition of expression of proinflammatory mediators, such as TNF alpha and COX-2, in inflamed tissues.Conclusion. These studies further establish NF-kappa B as a target for antiinflammatory therapy and provide support for the use of the NBD peptide as a possible therapeutic agent for inflammatory diseases.