TRAF3抑制IL-17引起的软骨破坏作用

目的研究肿瘤坏死因子受体相关因子3（TRAF3）对白介素-17（IL-17）刺激的软骨细胞中丝裂原激活蛋白激酶（MAPK）和核因子-κB（NF-κB）信号通路及其下游产物表达的影响；观察TRAF3转基因小鼠IL-17刺激的关节软骨破坏情况，探讨TRAF3的软骨保护作用。方法Westernblotting检测正常软骨细胞和TRAF5基因过表达软骨细胞中IL-17刺激的MAPK和NF-κB信号通路的变化，Real-TimePCR检测正常软骨细胞和TRAF3基因过表达软骨细胞中IL-17刺激的下游炎症因子IL-6、基质金属蛋白酶-13（MMP13）、含I型血小板结合蛋白基序的解聚蛋白样金属蛋白酶-4...

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Bibliographic Details
Published in上海交通大学学报：医学版 Vol. 34; no. 7; pp. 984 - 989
Main Author 张宁 刘宏强 赵小英 童文学 张晓玲
Format Journal Article
LanguageChinese
Published 2014
Subjects
炎症
白介素-17
肿瘤坏死因子受体相关因子3
软骨保护
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Summary:目的研究肿瘤坏死因子受体相关因子3（TRAF3）对白介素-17（IL-17）刺激的软骨细胞中丝裂原激活蛋白激酶（MAPK）和核因子-κB（NF-κB）信号通路及其下游产物表达的影响；观察TRAF3转基因小鼠IL-17刺激的关节软骨破坏情况，探讨TRAF3的软骨保护作用。方法Westernblotting检测正常软骨细胞和TRAF5基因过表达软骨细胞中IL-17刺激的MAPK和NF-κB信号通路的变化，Real-TimePCR检测正常软骨细胞和TRAF3基因过表达软骨细胞中IL-17刺激的下游炎症因子IL-6、基质金属蛋白酶-13（MMP13）、含I型血小板结合蛋白基序的解聚蛋白样金属蛋白酶-4（ADAMTS-4）和ADAMTS．5mRNA的表达变化，组织化学技术观察注射IL-17野生型小鼠与TRAF3转基因小鼠关节软骨变化的差异。结果TRAF3的过表达能显著抑制经IL-17刺激软骨细胞中MAPK和NF-κB信号通路，使下游炎症因子IL-6、MMP13、ADAMTS．4和ADAMTS-5mRNA的表达显著下调；TRAF3转基因小鼠IL-17引起的关节软骨降解显著较野生型小鼠减轻。结论作为IL-17信号通路的负调控抑制剂，TRAF3可能成为抑制关节炎软骨破坏的新靶点。
Bibliography:Objective To investigate the effects of TNF receptor associated factor 3 （TRAF3） on signaling pathways and expressions of downstream products of MAPK and NF-κB in chondrocytes stimulated by the interleukin-17 （IL-17） ; to observe the cartilage destruction of TRAF3 transgenic mice stimulated by the IL-17; and to explore the protective effect of TRAF3 on the cartilage. Methods Changes of signaling pathways of NF-κB and MAPK in normal chondrocytes and TRAF3 transgenic chondrocytes stimulated by the IL-17 were detected by the Western blotting. The changes of mRNA of downstream inflammatory factor IL-6, metabolic factors MMP13, disintegrin and metalloproteinase with thrombospondin motif4 （ADAMTS-4）, and ADAMTS- 5 in normal chondrocytes and TRAF3 transgenic chondrocytes stimulated by the IL-17 were detected by the Real-Time PCR. Differences of cartilage changes of wildtype mice and TRAF3 transgenic mice stimulated by the IL-17 were observed by the histochemistry. Results The over-expression of TRAF3 significandy in
ISSN:1674-8115