Acidic pH-induced elevation in interleukin 8 expression by human ovarian carcinoma cells

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Interleukin 8 (IL-8) expression in ovarian cancer correlates with disease progression.
• The extracellular tumor microenvironment is often acidic due to metabolic byproducts.
• The precise mechanisms regulating IL-8 induction in acidic conditions remain unclear.

Purpose of the Study:

• To investigate the effect of acidic extracellular pH on IL-8 expression in human ovarian cancer cells.
• To elucidate the molecular mechanisms underlying IL-8 gene regulation by acidosis.

Main Methods:

• Culturing SKOV3 ip1 ovarian cancer cells in acidic medium (pH 6.6).
• Quantifying IL-8 mRNA and protein levels using Northern blot and ELISA.
• Analyzing the IL-8 promoter using functional analysis and luciferase reporter studies.
• Assessing transcription factor binding via electrophoretic mobility shift assay (EMSA).

Main Results:

• Acidic conditions significantly increased IL-8 mRNA and protein expression.
• Acidosis-mediated IL-8 induction involved both transcriptional activation and mRNA stabilization.
• A specific region (-133 to -98 bp) of the IL-8 promoter was crucial for transcriptional activation.
• Acidic pH activated activator protein-1 (AP-1) and nuclear factor-kappaB (NF-kappaB)-like factors, which bound to the IL-8 promoter.

Conclusions:

• Acidic extracellular pH is a significant regulator of IL-8 gene expression in ovarian cancer cells.
• The activation of AP-1 and NF-kappaB transcription factors by acidic pH contributes to increased IL-8 production.
• Understanding this mechanism may offer novel therapeutic targets for ovarian cancer treatment.