Regulation of Interleukin-8 Expression by Cellular pH in Human Pancreatic Adenocarcinoma Cells

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Abstract
The role of cellular pH in the expression and regulation of interleukin-8 (IL-8) in human tumor cell lines was determined. Transient exposure to pH ranging from 7.4 to 6.7 induced pH-dependent expression of IL-8 at both the mRNA and protein levels in three different human tumor cell lines, including COLO357 pancreatic adenocarcinoma cells, SW620 colon adenocarcinoma cells, and PC3 prostate adenocarcinoma cells. Investigation of the mechanisms of IL-8 induction in response to acidosis was carried out using the COLO357 human pancreatic cancer cell line. The increased steady-state level of mRNA correlated with an increased transcription rate and stability of IL-8 transcripts. Further experiments indicated that mild acidosis activated the transcription factors NF-κB and AP-1 and that the cooperation of these two factors appeared to be essential to the transactivation of the IL-8 gene. Our data demonstrated that low tumor pH contributes to the enhanced expression of IL-8 and plays an important role in tumor progression.