Pancreas-specific RelA/p65 truncation increases susceptibility of acini to inflammation-associated cell death following cerulein pancreatitis
Pancreas-specific RelA/p65 truncation increases susceptibility of acini to inflammation-associated cell death following cerulein pancreatitis
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DOI：
10.1172/jci29882
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发表时间：
2007-06-01
影响因子：
15.9
通讯作者：
Schmid, Roland M.
中科院分区：
文献类型：
--
作者：
Algul, Hana;Treiber, Matthias;Schmid, Roland M.
转录因子 NF-kappa B/Rel 的激活已被证明与炎症性疾病有关。在这里，我们使用 Cre-loxP 策略研究了主要反式激活亚基 RelA/p65 在急性胰腺炎期间的作用。选择性截断胰腺外分泌细胞中的 rela 基因会导致腺泡细胞严重损伤和包括肺和肝损伤在内的全身并发症。我们的数据表明，保护性胰腺特异性急性期蛋白胰腺炎相关蛋白 I (PAPI) 的表达和诱导取决于 RelA/p65。 PAP1 cDNA 的慢病毒基因转移减少了选择性截短 RelA/p65 的小鼠胰腺的坏死和浸润程度。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-kappa B/Rel 的胰腺特异性作用，并表明 NF-kappa B/Rel 在炎症过程中不同细胞和环境中的多维作用。
Activation of the transcription factor NF-kappa B/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 I (PAPI) 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-kappa B/Rel and suggest multidimensional roles of NF-kappa B/Rel in different cells and contexts during inflammation.