The Expression of Chemokine Genes Correlates with Nuclear Factor-&kgr;B Activation in Human Pancreatic Cancer Cell Lines
The Expression of Chemokine Genes Correlates with Nuclear Factor-&kgr;B Activation in Human Pancreatic Cancer Cell Lines
复制标题
趋化因子基因的表达与核因子相关
作者：
H. Takaya;A. Andoh;M. Shimada;K. Hata;Y. Fujiyama;T. Bamba
趋化因子可以调节免疫细胞浸润的过程，这通常在胰腺癌中发现。在这项研究中，我们研究了趋化因子[白细胞介素（IL）-8，MCP-1和RANTES（调节激活，正常T细胞表达和分泌）]在人胰腺癌细胞系中的分泌。采用酶联免疫吸附试验（ELISA）和北方印迹法（Northern blot）检测胰腺癌细胞株PANC-1、MIA PaCa-2和BxPC-3趋化因子的分泌，凝胶迁移率变动试验（EMSA）检测核因子-B（NF-B）和NF-IL 6的活化。在没有任何刺激的情况下，在所有细胞系中检测到IL-8分泌，并且在PANC-1和MIA PaCa-2细胞中检测到MCP-1分泌。然而，在所有细胞中未检测到RANTES分泌。IL-1和肿瘤坏死因子（TNF）的加入强烈增强IL-8，MCP-1和RANTES分泌，这些反应在mRNA水平以及在蛋白质水平观察。IL-1和TNF-α可诱导PANC-1细胞核因子（NF）- B的快速活化，且趋化因子mRNA表达的增加与NF-B的活化相关。NF-IL 6的活化是适度的。TPCK阻断NF-B活化可显著降低IL-1和TNF-α诱导的趋化因子基因表达。我们的研究结果表明，趋化因子是由胰腺癌细胞产生的，并表明这些因素可能有助于肿瘤相关免疫细胞的积累。此外，胰腺癌细胞中趋化因子基因的转录激活可能与NF-B激活密切相关。
Chemokines may regulate the process of immune cell infiltration that is often found in pancreatic cancer. In this study, we investigated the secretion of the chemokines [interleukin (IL)-8, monocyte chemoattractant protein (MCP)-1, and RANTES (regulated on activation, normal T cell expressed and secreted)] in human pancreatic cancer cell lines. The chemokine secretion in three pancreatic cancer cell lines (PANC-1, MIA PaCa-2, and BxPC-3) was evaluated by enzyme-linked immunosorbent assay (ELISA) and Northern blot, and the activation of nuclear factor-&kgr;B (NF-&kgr;B) and NF-IL6 was assessed by an electrophoretic gel mobility shift assay (EMSA). Without any stimulation, IL-8 secretion was detected in all cell lines, and MCP-1 secretion was detected in PANC-1 and MIA PaCa-2 cells. However, RANTES secretion was not detected in all cells. The addition of IL-1&bgr; and tumor necrosis factor (TNF)-&agr; strongly enhanced IL-8, MCP-1, and RANTES secretion; these responses were observed at the mRNA level as well as at the protein level. IL-1&bgr; and TNF-&agr; induced a rapid activation of nuclear factor (NF)-&kgr;B in PANC-1 cells, and the increase in chemokine mRNA expression correlated with NF-&kgr;B activation. The activation of NF-IL6 was modest. A blockade of NF-&kgr;B activation by TPCK markedly reduced the IL-1&bgr;- and TNF-&agr;–induced chemokine gene expression. Our findings indicate that chemokines are produced by pancreatic cancer cells, and suggest that these factors may contribute to the accumulation of tumor-associated immune cells. In addition, the transcriptional activation of chemokine genes in pancreatic cancer cells may be closely associated with NF-&kgr;B activation.
影响因子：
29.4
作者：
ECKMANN, L;JUNG, HC;KAGNOFF, MF
通讯作者：
KAGNOFF, MF
影响因子：
29.4
作者：
Grady, T;Liang, P;Logsdon, CD
通讯作者：
Logsdon, CD