Olive oil phenolic extract regulates interleukin-8 expression by transcriptional and post-transcriptional mechanisms in Caco-2 cells

In this study we investigated the ability of a phenolic extract from extra virgin olive oil (OPE) to modulate the inflammatory response in intestinal epithelial cells. Undifferentiated and differentiated Caco-2 cells were challenged with LPS (50 μg/ml) or IL-1β (5 ng/ml) to mimic the early and intermediate phase of intestinal inflammation, respectively. The effects of OPE on NF-κB-driven transcription and IL-8 promoter activity were evaluated in transfection assays, coupled to p65 nuclear translocation. Modulation of IL-8 mRNA levels by OPE was measured by quantitative RT-PCR while effects on protein levels by ELISA. Specific MAPKs inhibitors were used to investigate mRNA stability and the involvement of related signalling pathways. OPE prevented IL-8 expression and secretion in LPS-treated Caco-2 cells. In the presence of IL-1β OPE exhibited opposing effects on IL-8 gene transcription and mRNA/protein levels. While in IL-1β-treated cells IL-8 promoter activity was inhibited by treatment with OPE, IL-8 mRNA stability was strongly enhanced, leading to increased protein expression. Inhibitors of p38 and ERKs partly prevented OPE effect on IL-8 mRNA levels. Intestinal epithelial cells represent a direct target of the action of olive oil phenols where they regulate IL-8 expression by transcriptional and post-transcriptional mechanisms.