Cytokine regulation of chemokine (IL-8, MCP-1, and RANTES) gene expression in human pancreatic periacinar myofibroblasts
Cytokine regulation of chemokine (IL-8, MCP-1, and RANTES) gene expression in human pancreatic periacinar myofibroblasts
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DOI：
10.1053/gast.2000.8538
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发表时间：
2000-07-01
期刊：
影响因子：
29.4
通讯作者：
Bamba, T
中科院分区：
文献类型：
--
作者：
Andoh, A;Takaya, H;Bamba, T
背景和目标：我们以前分离和鉴定了人胰腺腺泡周围肌成纤维细胞，在本研究中，为了确定这些细胞在急性胰腺炎发病机制中的作用，我们研究了它们中的趋化因子表达。研究方法：通过ELISA、北方印迹和核连续试验评价趋化因子（白细胞介素[IL]-8、单核细胞趋化蛋白[MCP]-1、RANTES和MIP [巨噬细胞炎性蛋白]-1 α）的分泌。通过电泳凝胶迁移率变动试验评价NF-κ B和NF-IL 6的活化。结果：IL-1 β和肿瘤坏死因子（TNF）-α均可快速诱导IL-8和MCP-1分泌。RANTES分泌诱导更慢，主要由TNF-α诱导。然而，MIP-1 α分泌不受任何刺激诱导。在信使RNA水平也观察到这些反应，并且它们伴随着转录速率的增加。趋化因子基因转录激活的增加与NF-κ B和NF-IL 6激活相关。此外，通过PDTC和TPCK阻断NF-κ B活化可显著降低IL-1 β或TNF-α诱导的趋化因子基因表达。结论：胰腺腺泡周围肌成纤维细胞的趋化因子分泌受到不同的调节，表明这些细胞在介导胰腺中炎性细胞的浸润和积累中发挥作用。
Background & Aims: We have previously isolated and characterized human pancreatic periacinar myofibroblasts, in this study, to define the role of these cells in the pathogenesis of acute pancreatitis, we investigated chemokine expression in them. Methods: Secretion of chemokines (interlerkin [IL]-8, monocyte chemoattractant protein [MCP]-1, RANTES, and MIP [macrophage inflammatory protein]-1 alpha) was evaluated by ELISA, Northern blotting, and nuclear run-on assays, The activation of NF-kappa B and NF-IL6 was assessed by an electrophoretic gel mobility shift assay. Results: IL-8 and MCP-1 secretion was rapidly induced by both IL-1 beta and tumor necrosis factor (TNF)-alpha. RANTES secretion was induced more slowly and was induced mainly by TNF-alpha. However, MIP-1 alpha secretion was not induced by any stimuli. These responses were also observed at the messenger RNA level, and they were accompanied by an increase in transcriptional rate. The increase in transcriptional activation of chemokine genes correlated with the NF-kappa B and NF-IL6 activation. Furthermore, a blockade of NF-kappa B activation by PDTC and TPCK markedly reduced the IL-1 beta- or TNF-alpha-induced chemokine gene expression. Conclusions: Chemokine secretion is differentially regulated in pancreatic periacinar myofibroblasts, suggesting a role for these cells in mediating the infiltration and accumulation of inflammatory cells in the pancreas.