Chemokine gene expression in rat pancreatic acinar cells is an early event associated with acute pancreatitis
Chemokine gene expression in rat pancreatic acinar cells is an early event associated with acute pancreatitis
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DOI：
10.1016/s0016-5085(97)70017-9
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发表时间：
1997-12-01
期刊：
影响因子：
29.4
通讯作者：
Logsdon, CD
中科院分区：
文献类型：
--
作者：
Grady, T;Liang, P;Logsdon, CD
背景与目的：胰腺炎的分子机制尚不清楚。这项研究的目的是确定与胰腺炎相关的早期遗传事件。方法：应用差异显示技术对正常胰腺和促分泌素诱导的胰腺炎胰腺组织进行mRNA的差异显示。用克隆的趋化因子互补DNA探测正常动物和实验性急性胰腺炎动物的北方印迹。用蛙皮素和逆行注射胆盐诱导胰腺炎。免疫细胞化学方法鉴定趋化因子表达的来源。测试吡咯烷二硫代氨基甲酸酯对趋化因子表达和胰腺炎的影响。结果：雨蛙肽过度刺激后早期始终观察到差异扩增条带。这条带被鉴定为mob-1基因的一部分，一种α-趋化因子。北方分析表明，mob-1和另一种趋化因子mcp-1的mRNA在雨蛙肽过度刺激后被诱导。胆盐逆行注射和雨蛙肽对体外培养的腺泡细胞中mob-1 mRNA的表达也有诱导作用。MOB-1蛋白定位于胰腺外分泌细胞。吡咯烷二硫代氨基甲酸酯抑制趋化因子基因表达和胰腺炎的早期炎症特征。结论：趋化因子通过诱导胰腺炎的治疗在腺泡细胞中被诱导，并且可能在疾病的早期阶段起重要作用。
Background & Aims: The molecular mechanisms underlying pancreatitis are largely unknown. The goal of this study was to identify an early genetic event that correlated with pancreatitis. Methods: Differential display of messenger RNAs (mRNAs) was conducted on normal pancreas vs. those of animals with secretagogue-induced pancreatitis. Northern blots from normal animals and animals with experimental acute pancreatitis were probed with cloned complementary DNAs for chemokines. Pancreatitis was induced with cerulein and by retrograde injection of bile salts. Immunocytochemistry was used to identify the source of chemokine expression. Pyrrolidine dithiocarbamate was tested for effects on chemokine expression and pancreatitis. Results: A differentially amplified band was consistently observed early after cerulein hyperstimulation. This band was identified as a portion of the mob-1 gene, an alpha-chemokine. Northern analysis indicated that mRNAs for mob-1 and another chemokine, mcp-1, were induced after cerulein hyperstimulation in vivo. mob-1 mRNA was also induced by retrograde injection of bile salts and by cerulein in acinar cells in vitro. mob-1 protein was localized to exocrine cells in pancreata of diseased animals. Pyrrolidine dithiocarbamate inhibited both chemokine gene expression and early inflammatory characteristics of pancreatitis. Conclusions: Chemokines are induced in acinar cells by treatments that induce pancreatitis and may play an important role in the early stages of the disease.