The expression of chemokine genes correlates with nuclear factor-kappa B activation in human pancreatic cancer cell lines

Chemokines may regulate the process of immune cell infiltration that is oft en found in pancreatic cancer. In this study, we investigated the secretion of the chemokines [interleukin (IL)-8, monocyte chemoattractant protein (M CP)-1, and RANTES (regulated on activation, normal T cell expressed and sec reted)] in human pancreatic cancer cell lines. The chemokine secretion in t hree pancreatic cancer cell lines (PANC-1, MIA PaCa-2, and BxPC-3) was eval uated by enzyme-linked immunosorbent assay (ELISA) and Northern blot, and t he activation of nuclear factor-kappa B (NF-kappa B) and NF-IL6 was assesse d by an electrophoretic gel mobility shift assay (EMSA). Without any stimul ation, IL-8 secretion was detected in all cell lines, and MCP-1 secretion w as detected in PANC-1 and MIA PaCa-2 cells. However, RANTES secretion was n ot detected in all cells. The addition of IL-I beta and tumor necrosis fact or (TNF)-alpha strongly enhanced IL-8, MCP-I, and RANTES secretion; these r esponses were observed at the mRNA level as well as at the protein level. I L-I beta and TNF-alpha induced a rapid activation of nuclear factor (NF)-ka ppa B in PANC-1 cells, and the increase in chemokine mRNA expression correl ated with NF-kappa B activation. The activation of NF-IL6 was modest. A blo ckade of NF-kappa B activation by TPCK markedly reduced the IL-1 beta and T NF-alpha-induced chemokine gene expression. Our findings indicate that chem okines are produced by pancreatic cancer cells, and suggest that these fact ors 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-kappa B activation.