TNF-alpha mediated NF-kappaB activation is constantly extended by transglutaminase 2.
TNF-alpha mediated NF-kappaB activation is constantly extended by transglutaminase 2.
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DOI：
10.2741/e249
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发表时间：
2011-01-01
期刊：
影响因子：
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通讯作者：
Kim, Soo-Youl
中科院分区：
文献类型：
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作者：
Park, Kang-Seo;Kim, Dae-Seok;Kim, Soo-Youl
在许多炎性疾病以及耐药癌细胞中已经报道了转氨酶2（TGase 2）表达水平的增加。先前的报道已经表明，TGase 2能够在不存在I-kappaB α激酶活化的情况下通过聚合耗尽kappaB（I-kappaB）α的抑制剂来诱导核因子-kappaB（NF-kappaB）活化。这就提出了一个问题，即TGase 2的表达增加是否可以延长经典活化途径介导的NF-κ B活化。在TGase 2诱导的EcR 23/TG细胞系中，TGase 2过表达导致在TNF-α存在下NF-κ B的持续活化长达24小时，而在不存在TGase 2诱导的情况下，NF-κ B活性在TNF-α处理6小时内恢复到基础水平。在用表达TGase 2的腺病毒载体注射的小鼠中，NF-κ B被组成性激活长达5天，而Adeno/GFP注射的小鼠在响应TNF-α应激时表现出NF-κ B的减弱激活。因此，TG酶2水平升高可能会加剧炎症状态下NF-κ B的活化。
Increased levels of transglutaminase 2 (TGase 2) expression have been reported in many inflammatory diseases, as well as in drug resistant cancer cells. Previous reports have shown that TGase 2 is capable of inducing nuclear factor-kappaB (NF-kappaB) activation via depletion of inhibitor of kappaB (I-kappaB)alpha through polymerization in the absence of I-kappaBalpha kinase activation. This raises the question of whether increased expression of TGase 2 can extend NF-kappaB activation mediated by a canonical activation pathway. In the TGase 2-inducible EcR23/TG cell line, TGase 2 over-expression resulted in sustained activation of NF-kappa B in the presence of TNF-alpha, for up to 24 hrs, while in the absence of TGase 2 induction, NF-kappaB activity was restored to basal levels within 6 hrs of TNF-alpha treatment. In mice injected with an adenovirus vector expressing TGase 2, NF-kappaB was constitutively activated for up to 5 days, whereas Adeno/GFP-injected mice exhibited attenuated activation of NF-kappaB in response to TNF-alpha stress. Thus, the presence of increased levels of TGase 2 may exacerbate NF-kappa B activation in inflammatory states.