Algül Hana, Treiber Matthias, Lesina Marina, Nakhai Hassan, Saur Dieter, Geisler Fabian, Pfeifer Alexander, Paxian Stephan, Schmid Roland M
Second Department of Internal Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
J Clin Invest. 2007 Jun;117(6):1490-501. doi: 10.1172/JCI29882. Epub 2007 May 24.
Activation of the transcription factor NF-kappaB/Rel has been shown to be involved in inflammatory disease. Here we studied the role of RelA/p65, the main transactivating subunit, during acute pancreatitis using a Cre-loxP strategy. Selective truncation of the rela gene in pancreatic exocrine cells led to both severe injury of the acinar cells and systemic complications including lung and liver damage. Our data demonstrated that expression and induction of the protective pancreas-specific acute phase protein pancreatitis-associated protein 1 (PAP1) depended on RelA/p65. Lentiviral gene transfer of PAP1 cDNA reduced the extent of necrosis and infiltration in the pancreata of mice with selective truncation of RelA/p65. These results provide in vivo evidence for RelA/p65 protection of acinar cell death via upregulation of PAP1. Moreover, our data underscore the pancreas-specific role of NF-kappaB/Rel and suggest multidimensional roles of NF-kappaB/Rel in different cells and contexts during inflammation.
转录因子NF-κB/Rel的激活已被证明与炎症性疾病有关。在此，我们使用Cre-loxP策略研究了主要反式激活亚基RelA/p65在急性胰腺炎中的作用。胰腺外分泌细胞中rela基因的选择性截短导致腺泡细胞严重损伤以及包括肺和肝损伤在内的全身并发症。我们的数据表明，胰腺特异性急性期蛋白胰腺炎相关蛋白1（PAP1）的表达和诱导依赖于RelA/p65。PAP1 cDNA的慢病毒基因转移减少了RelA/p65选择性截短的小鼠胰腺中的坏死和浸润程度。这些结果为RelA/p65通过上调PAP1保护腺泡细胞死亡提供了体内证据。此外，我们的数据强调了NF-κB/Rel在胰腺中的特异性作用，并表明NF-κB/Rel在炎症过程中不同细胞和环境中具有多维度作用。
