Regulation of interleukin-8 expression by nitric oxide in human pancreaticadenocarcinoma

The regulation of interleukin-8 (IL-8) expression by nitric oxide (NO) was determined in human pancreatic cancer cell lines. CaPan-2 and FG human panc reatic adenocarcinoma cells were incubated for 24 h in medium alone or medi um containing a cytokine mixture in the presence or absence of an NO syntha se (NOS) inhibitor, N-G-monomethyl-L-arginine (NMA). The NOS activity and l evel of IL-8 expression were determined. IL-8 expression was induced in the two cell lines. A low level of NOS activity was detectable only in CaPan-2 cells. Moreover, the presence of NMA did not reverse the induction of IL-8 . The FG cells were then engineered to produce a physiologic level of NO an d incubated in medium alone or medium containing 1 mM NMA. No significant I L-8 expression was induced in those producing a low level of NO, whereas IL -8 expression was induced in those producing a high level of NO. Inhibition of NO production by NMA reversed this effect. Incubation of FG cells with an NO donor, S-nitroso-D,L.-acetyl-penicillamine (SNAP), led to a concentra tion-dependent and time-dependent induction of IL-8 expression. This NO-med iated upregulation of IL-8 expression correlated with an increase in IL-8 g ene transcription and mRNA stability. Our results indicate that NO is invol ved in the regulation of IL-8 expression in and contributes to the progress ion of human pancreatic cancer.