Suppression of IL-1β expression by the Jak 2 inhibitor AG490 in cerulein-stimulated pancreatic acinar cells
Suppression of IL-1β expression by the Jak 2 inhibitor AG490 in cerulein-stimulated pancreatic acinar cells
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DOI：
10.1016/j.bcp.2006.07.008
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发表时间：
2006-11
影响因子：
5.8
通讯作者：
J. Yu;K. Kim;Hyeyoung Kim
中科院分区：
文献类型：
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作者：
J. Yu;K. Kim;Hyeyoung Kim
雨蛙肽胰腺炎与人水肿性胰腺炎相似，具有消化酶产生失调和胞质空泡化、腺泡细胞死亡、水肿形成和炎性细胞浸润到胰腺中。细胞因子在蛙皮素刺激的胰腺腺泡细胞中上调。在各种细胞和组织中，Janus激酶（Jak）/信号转导和转录激活因子（Stat）途径介导炎症过程。在本研究中，我们研究了Jak/Stat信号通路的激活是否介导了体外用雨蛙肽刺激的胰腺腺泡AR 42 J细胞以及体内使用Jak 2抑制剂AG 490的雨蛙肽胰腺炎大鼠中IL-1β的表达。通过Western印迹分析磷酸化的Jak 2和磷酸化的Stat 3来监测Jak 2和Stat 3的活化。采用逆转录-聚合酶链反应（RT-PCR）和酶联免疫吸附试验（ELISA）检测IL-1β mRNA和蛋白水平。取胰腺组织行组织学检查，ELISA法测定血清IL-1β水平。结果表明，雨蛙肽可诱导AR 42 J细胞Jak 2和Stat 3的活化以及IL-1β的表达，而AG 490可抑制IL-1 β的表达。AG 490可抑制蛙皮性胰腺炎大鼠胰腺水肿和炎症改变，并抑制血清IL-1β水平升高。结论：Jak 2/Stat 3信号通路可能是胰腺炎发病机制中的一个重要环节，可能通过诱导IL-1β等细胞因子而发挥作用。
Cerulein pancreatitis is similar to human edematous pancreatitis with dysregulation of the digestive enzyme production and cytoplasmic vacuolization, the death of acinar cells, edema formation, and an infiltration of inflammatory cells into the pancreas. Cytokines are up-regulated in pancreatic acinar cells stimulated with cerulein. In various cells and tissues, Janus kinase (Jak)/signal transducer and activator of transcription (Stat) pathway mediates inflammatory process. In the present study, we investigated whether the activation of Jak/Stat signaling mediates IL-1β expression in pancreatic acinar AR42J cells stimulated with cerulein in vitro as well as the rats with cerulein pancreatitis in vivo using AG490, the Jak2 inhibitor. Activation of Jak2 and Stat3 were monitored by Western blot analysis for phosphorylated Jak2 and phosphorylated Stat3. mRNA expression and protein level of IL-1β were determined by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbant assay (ELISA). Histological examination of pancreatic tissues were performed and serum IL-1β levels of the rats were determined by ELISA. As a result, cerulein induced the activation of Jak2 and Stat3 as well as IL-1β expression, which was inhibited by the treatment of AG490 in AR42J cells. In cerulein pancreatitis of the rats, edematous and inflammatory changes of the pancreas and increased serum levels of IL-1β were suppressed by AG490 treatment. In conclusion, Jak2/Stat3 pathway may be the underlying mechanism in the pathogenesis of pancreatitis by inducing cytokines such as IL-1β.