Olive oil phenolic extract regulates interleukin‐8 expression by transcriptional and posttranscriptional 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 nuclear factor‐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 mitogen activated protein kinases inhibitors were used to investigate mRNA stability and the involvement of related signaling 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 extracellular signal‐regulated kinases 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 posttranscriptional mechanisms.