白细胞介素8（IL-8）和P物质在人类慢性胰腺炎中的表达。
Expression of interleukin 8 (IL-8) and substance P in human chronic pancreatitis.
作者信息
Di Sebastiano P, di Mola F F, Di Febbo C, Baccante G, Porreca E, Innocenti P, Friess H, Büchler M W
机构信息
Department of Visceral and Transplantation Surgery, University of Bern, Inselspital, Switzerland.
出版信息
Gut. 2000 Sep;47(3):423-8. doi: 10.1136/gut.47.3.423.
BACKGROUND
Changes in substance P content and a relationship between the degree of perineural inflammation and pain has been demonstrated in chronic pancreatitis. Whether a relationship exists between neural alteration and pancreatic inflammation (neurogenic inflammation) is not known.
AIMS
In the present study we evaluated gene expression of preprotachykinin A (PPT-A), the gene encoding substance P, and interleukin 8, a proinflammatory and hyperalgesic mediator whose release is co-regulated by substance P.
PATIENTS
Pancreatic tissue specimens obtained from 21 patients (16 male, five female) with chronic pancreatitis and 18 healthy organ donors (nine male, nine female) were analysed.
METHODS
Gene expression of PPT-A and interleukin 8 was studied by northern blot analysis. Respective proteins were localised using immunohistochemistry.
RESULTS
Northern blot analysis showed that PTT-A mRNA expression levels were present at comparable levels in normal and chronic pancreatitis tissue samples. In contrast, interleukin 8 mRNA was expressed at very low levels in normal controls but was increased 41-fold (p<0. 001) in chronic pancreatitis tissue samples. Using immunohistochemistry, interleukin 8 protein was localised mainly in immune cells often found around enlarged pancreatic nerves. In addition, in chronic pancreatitis, intense interleukin 8 immunostaining was present in metaplastic ductal cells of the atrophic pancreatic parenchyma. In chronic pancreatitis samples there was a positive relationship between interleukin 8 mRNA levels and the presence of ductal metaplasia (r=0.795; p<0.001) and the inflammation score (r=0.713; p<0.001).
CONCLUSIONS
Our data indicate that in chronic pancreatitis, the increase in substance P in enlarged pancreatic nerves is not caused by enhanced intrapancreatic PTT-A mRNA expression, suggesting that the location of substance P synthesis is outside of the pancreas. In addition, localisation of interleukin 8 positive immune cells around pancreatic nerves further supports the existence of neuroimmune interactions as a pathophysiological mechanism in chronic pancreatitis.
背景
慢性胰腺炎中已证实P物质含量的变化以及神经周围炎症程度与疼痛之间的关系。神经改变与胰腺炎症（神经源性炎症）之间是否存在关联尚不清楚。
目的
在本研究中，我们评估了前速激肽原A（PPT-A）的基因表达，P物质的编码基因，以及白细胞介素8，一种促炎和痛觉过敏介质，其释放由P物质共同调节。
患者
分析了从21例慢性胰腺炎患者（16例男性，5例女性）和18例健康器官供体（9例男性，9例女性）获取的胰腺组织标本。
方法
通过Northern印迹分析研究PPT-A和白细胞介素8的基因表达。使用免疫组织化学对相应蛋白质进行定位。
结果
Northern印迹分析显示，正常和慢性胰腺炎组织样本中PTT-A mRNA表达水平相当。相比之下，白细胞介素8 mRNA在正常对照中表达水平极低，但在慢性胰腺炎组织样本中增加了41倍（p<0.001）。使用免疫组织化学，白细胞介素8蛋白主要定位于常在扩大的胰腺神经周围发现的免疫细胞中。此外，在慢性胰腺炎中，萎缩性胰腺实质的化生导管细胞中存在强烈的白细胞介素8免疫染色。在慢性胰腺炎样本中，白细胞介素8 mRNA水平与导管化生的存在（r=0.795；p<0.001）和炎症评分（r=0.713；p<0.001）之间存在正相关。
结论
我们的数据表明，在慢性胰腺炎中，扩大的胰腺神经中P物质的增加不是由胰腺内PTT-A mRNA表达增强引起的，这表明P物质合成的位置在胰腺外。此外，胰腺神经周围白细胞介素8阳性免疫细胞的定位进一步支持了神经免疫相互作用作为慢性胰腺炎病理生理机制的存在。
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