Ligation of the Fas antigen stimulates chemokine secretion in pancreatic cancer cell line PANC-1.
OBJECTIVE
The role of chemokines in the process of immune cell infiltration into pancreatic cancer tissue has been reported. In this study, we investigated the induction of chemokines (interleukin (IL)-8 and monocyte chemoattractant protein (MCP)-1) by Fas antigen (Ag)-stimulation in a human pancreatic cancer cell line, PANC-1.


METHODS
The chemokine secretion was evaluated by using an ELISA and a northern blot, and the activation of nuclear factor-kappa B (NF-kappa B) was assessed by using an electrophoretic gel mobility shift assay (EMSA).


RESULTS
The Fas antigen (Ag) stimulation clearly induced an increase in IL-8 and MCP-1 secretion in PANC-1 cells. This effect was also observed at the mRNA level. The induction of chemokine secretion by Fas Ag stimulation required de novo gene expression and protein synthesis. The pretreatment with interferon (IFN)-gamma markedly enhanced the effects of Fas Ag stimulation; IFN-gamma pretreatment and Fas Ag stimulation synergistically induced not only apoptosis but also IL-8 and MCP-1 secretion. Flow cytometric analysis demonstrated that IFN-gamma significantly enhanced Fas Ag expression. In addition, Fas Ag stimulation actually evoked NF-kappa B activation in this cell line.


CONCLUSIONS
Our results indicate that Fas Ag stimulation can induce chemokine secretion in PANC-1 cells, suggesting the contribution of Fas stimulation to the accumulation of immune cells in pancreatic cancer tissue.
Shimada
M
M
Department of Internal Medicine, Shiga University of Medical Science, Otsu, Japan.
Andoh
A
A
Araki
Y
Y
Fujiyama
Y
Y
Bamba
T
T
D000230:Adenocarcinoma / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology; D018932:Chemokine CCL2 / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D016209:Interleukin-8 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000276:immunology*; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000502:physiology*
D018932:Chemokine CCL2; D016209:Interleukin-8; D016328:NF-kappa B; D019014:fas Receptor; D007371:Interferon-gamma