NF-κB/Rel activation in cerulein pancreatitis
NF-κB/Rel activation in cerulein pancreatitis
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DOI：
10.1016/s0016-5085(99)70140-x
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发表时间：
1999-02-01
期刊：
影响因子：
29.4
通讯作者：
Schmid, RM
中科院分区：
文献类型：
--
作者：
Steinle, AU;Weidenbach, H;Schmid, RM
背景与目的：最近的证据表明，促分泌素诱导的胰腺炎期间启动了许多快速信号级联反应。然而，人们对核事件知之甚少。本研究的目的是探讨转录因子NF-κ B B/Rel的激活后，超最大刺激胆囊收缩素类似物雨蛙肽在胰腺。方法与结果：蛙皮素注射后15分钟，可检测到NF-κ B/Rel结合活性的核外观。DNA结合活性由NF-κ B1 p50、NF-κ B2 p52和RelA p65组成，如通过supershift测定和Western印迹分析所判断的。NF-κ B/Rel激活的开始和终止与I κ B α的降解和再现相关。蛙皮素在体外以超最大剂量激活NF-κ B/Rel，但在生理剂量下不激活。在用吡咯烷二硫代氨基甲酸酯阻断NF-κ B/Rel激活后，形态学改变的程度比对照组更明显，血清淀粉酶和乳酸脱氢酶水平显著升高，胰腺炎相关蛋白的信使RNA水平被更强烈地诱导，反映了更严重的胰腺炎程度。当N-乙酰-L-半胱氨酸被用作NF-κ B活化的抑制剂时，获得了类似的结果。结论：NF-κ B B/Rel在蛙皮素性胰腺炎中被迅速激活。这种激活可能在细胞损伤发生之前诱导自我防御的遗传程序，这可能防止促分泌素过度刺激后胰腺腺泡细胞的更高程度的损伤。
Background & Aims: Recent evidence suggests that a number of rapid signaling cascades are initiated during secretagogue-induced pancreatitis. However, little is known about the nuclear events. The aim of this study was to explore activation of the transcription factor NF-kappa B/Rel after supramaximal stimulation with the cholecystokinin analogue cerulein in the pancreas. Methods & Results: Nuclear appearance of NF-kappa B/Rel-binding activity was detectable 15 minutes after cerulein injection. The DNA-binding activity consisted of NF-kappa B1 p50, NF-kappa B2 p52, and RelA p65 as judged by supershift assays and Western blot analysis. The onset and termination of NF-kappa B/Rel activation correlated with the degradation and reappearance of I kappa B alpha. Cerulein in supramaximal but not in physiological doses activated NF-kappa B/Rel in vitro. After blocking of NF-kappa B/Rel activation with pyrrolidine dithiocarbamate, the degree of morphological alterations was more pronounced than in controls, serum amylase and lactate dehydrogenase levels were significantly increased, and messenger RNA levels of pancreatitis-associated protein were more strongly induced, reflecting a more severe degree of pancreatitis. Similar results were obtained when N-acetyl-L-cysteine was used as an inhibitor of NF-kappa B activation. Conclusions: These data show that NF-kappa B/Rel is rapidly activated during cerulein pancreatitis. This activation may induce a self-defending genetic program before the onset of cellular injury, which might prevent higher degrees of damage of pancreatic acinar cells after secretagogue hyperstimulation.